Maternal age at first birth and offspring criminality: using the children of twins design to test causal hypotheses.

PubMed

Coyne, Claire A; Långström, Niklas; Rickert, Martin E; Lichtenstein, Paul; D'Onofrio, Brian M

2013-02-01

Teenage childbirth is a risk factor for poor offspring outcomes, particularly offspring antisocial behavior. It is not clear, however, if maternal age at first birth (MAFB) is causally associated with offspring antisocial behavior or if this association is due to selection factors that influence both the likelihood that a young woman gives birth early and that her offspring engage in antisocial behavior. The current study addresses the limitations of previous research by using longitudinal data from Swedish national registries and children of siblings and children of twins comparisons to identify the extent to which the association between MAFB and offspring criminal convictions is consistent with a causal influence and confounded by genetic or environmental factors that make cousins similar. We found offspring born to mothers who began childbearing earlier were more likely to be convicted of a crime than offspring born to mothers who delayed childbearing. The results from comparisons of differentially exposed cousins, especially born to discordant monozygotic twin sisters, provide support for a causal association between MAFB and offspring criminal convictions. The analyses also found little evidence for genetic confounding due to passive gene-environment correlation. Future studies are needed to replicate these findings and to identify environmental risk factors that mediate this causal association.

Mendelian randomisation in type 2 diabetes and coronary artery disease.

PubMed

Frayling, Timothy M; Stoneman, Charli E

2018-06-20

Type 2 diabetes, coronary artery disease and hypertension are associated with anthropometric and biomarker traits, including waist-to-hip-ratio, body mass index and altered glucose and insulin levels. Clinical trials, for example of weight-loss interventions, show these factors are causal, but lifelong impact of subtle changes in body mass index and body fat distribution are less clear. The use of human genetics can quantify the causal effects of long-term exposure to subtle changes of modifiable risk factors. Mendelian randomisation (MR) uses human genetic variants associated with the risk factor to quantify the relationship between risk factor and disease outcome. The last two years have seen an increase in the number of MR studies investigating the relationship between anthropometric traits and metabolic diseases. This review provides an overview of these recent MR studies in relation to type 2 diabetes, coronary artery disease and hypertension. MR provides evidence for causal associations of waist-to-hip-ratio, body mass index and altered glucose levels with type 2 diabetes, coronary artery disease and hypertension. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Environmental risk factors for cancers of the brain and nervous system: the use of ecological data to generate hypotheses.

PubMed

de Vocht, Frank; Hannam, Kimberly; Buchan, Iain

2013-05-01

There is a public health need to balance timely generation of hypotheses with cautious causal inference. For rare cancers this is particularly challenging because standard epidemiological study designs may not be able to elucidate causal factors in an early period of newly emerging risks. Alternative methodologies need to be considered for generating and shaping hypotheses prior to definitive investigation. To evaluate whether open-access databases can be used to explore links between potential risk factors and cancers at an ecological level, using the case study of brain and nervous system cancers as an example. National age-adjusted cancer incidence rates were obtained from the GLOBOCAN 2008 resource and combined with data from the United Nations Development Report and the World Bank list of development indicators. Data were analysed using multivariate regression models. Cancer rates, potential confounders and environmental risk factors were available for 165 of 208 countries. 2008 national incidences of brain and nervous system cancers were associated with continent, gross national income in 2008 and Human Development Index Score. The only exogenous risk factor consistently associated with higher incidence was the penetration rate of mobile/cellular telecommunications subscriptions, although other factors were highlighted. According to these ecological results the latency period is at least 11-12 years, but probably more than 20 years. Missing data on cancer incidence and for other potential risk factors prohibit more detailed investigation of exposure-response associations and/or explore other hypotheses. Readily available ecological data may be underused, particularly for the study of risk factors for rare diseases and those with long latencies. The results of ecological analyses in general should not be overinterpreted in causal inference, but equally they should not be ignored where alternative signals of aetiology are lacking.

UNRECOGNIZED OR POTENTIAL RISK FACTORS FOR CHILDHOOD CANCER

EPA Science Inventory

Traditional epidemiological studies suggest that the contribution of environmental agents to childhood cancer may be minor. However, epidemiological methods can only seldom identify causal factors associated with a relative risk of less than a factor of one and a half to two. App...

Driver crash risk factors and prevalence evaluation using naturalistic driving data.

PubMed

Dingus, Thomas A; Guo, Feng; Lee, Suzie; Antin, Jonathan F; Perez, Miguel; Buchanan-King, Mindy; Hankey, Jonathan

2016-03-08

The accurate evaluation of crash causal factors can provide fundamental information for effective transportation policy, vehicle design, and driver education. Naturalistic driving (ND) data collected with multiple onboard video cameras and sensors provide a unique opportunity to evaluate risk factors during the seconds leading up to a crash. This paper uses a National Academy of Sciences-sponsored ND dataset comprising 905 injurious and property damage crash events, the magnitude of which allows the first direct analysis (to our knowledge) of causal factors using crashes only. The results show that crash causation has shifted dramatically in recent years, with driver-related factors (i.e., error, impairment, fatigue, and distraction) present in almost 90% of crashes. The results also definitively show that distraction is detrimental to driver safety, with handheld electronic devices having high use rates and risk.

Driver crash risk factors and prevalence evaluation using naturalistic driving data

PubMed Central

Dingus, Thomas A.; Guo, Feng; Lee, Suzie; Antin, Jonathan F.; Perez, Miguel; Buchanan-King, Mindy; Hankey, Jonathan

2016-01-01

The accurate evaluation of crash causal factors can provide fundamental information for effective transportation policy, vehicle design, and driver education. Naturalistic driving (ND) data collected with multiple onboard video cameras and sensors provide a unique opportunity to evaluate risk factors during the seconds leading up to a crash. This paper uses a National Academy of Sciences-sponsored ND dataset comprising 905 injurious and property damage crash events, the magnitude of which allows the first direct analysis (to our knowledge) of causal factors using crashes only. The results show that crash causation has shifted dramatically in recent years, with driver-related factors (i.e., error, impairment, fatigue, and distraction) present in almost 90% of crashes. The results also definitively show that distraction is detrimental to driver safety, with handheld electronic devices having high use rates and risk. PMID:26903657

[Eco-epidemiology: towards epidemiology of complexity].

PubMed

Bizouarn, Philippe

2016-05-01

In order to solve public health problems posed by the epidemiology of risk factors centered on the individual and neglecting the causal processes linking the risk factors with the health outcomes, Mervyn Susser proposed a multilevel epidemiology called eco-epidemiology, addressing the interdependence of individuals and their connection with molecular, individual, societal, environmental levels of organization participating in the causal disease processes. The aim of this epidemiology is to integrate more than a level of organization in design, analysis and interpretation of health problems. After presenting the main criticisms of risk-factor epidemiology focused on the individual, we will try to show how eco-epidemiology and its development could help to understand the need for a broader and integrative epidemiology, in which studies designed to identify risk factors would be balanced by studies designed to answer other questions equally vital to public health. © 2016 médecine/sciences – Inserm.

The relationship of family characteristics and bipolar disorder using causal-pie models.

PubMed

Chen, Y-C; Kao, C-F; Lu, M-K; Yang, Y-K; Liao, S-C; Jang, F-L; Chen, W J; Lu, R-B; Kuo, P-H

2014-01-01

Many family characteristics were reported to increase the risk of bipolar disorder (BPD). The development of BPD may be mediated through different pathways, involving diverse risk factor profiles. We evaluated the associations of family characteristics to build influential causal-pie models to estimate their contributions on the risk of developing BPD at the population level. We recruited 329 clinically diagnosed BPD patients and 202 healthy controls to collect information in parental psychopathology, parent-child relationship, and conflict within family. Other than logistic regression models, we applied causal-pie models to identify pathways involved with different family factors for BPD. The risk of BPD was significantly increased with parental depression, neurosis, anxiety, paternal substance use problems, and poor relationship with parents. Having a depressed mother further predicted early onset of BPD. Additionally, a greater risk for BPD was observed with higher numbers of paternal/maternal psychopathologies. Three significant risk profiles were identified for BPD, including paternal substance use problems (73.0%), maternal depression (17.6%), and through poor relationship with parents and conflict within the family (6.3%). Our findings demonstrate that different aspects of family characteristics elicit negative impacts on bipolar illness, which can be utilized to target specific factors to design and employ efficient intervention programs. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Genetic Instrumental Variable Studies of Effects of Prenatal Risk Factors

PubMed Central

von Hinke Kessler Scholder, Stephanie

2013-01-01

Identifying the effects of maternal risk factors during pregnancy on infant and child health is an area of tremendous research interest. However, of interest to policy makers is unraveling the causal effects of prenatal risk factors, not their associations with child health, which may be confounded by several unobserved factors. In this paper, we evaluate the utility of genetic variants in three genes that have unequivocal evidence of being related to three major risk factors – CHRNA3 for smoking, ADH1B for alcohol use, and FTO for obesity – as instrumental variables for identifying the causal effects of such factors during pregnancy. Using two independent datasets, we find that these variants are overall predictive of the risk factors and are not systematically related to observed confounders, suggesting that they may be useful instruments. We also find some suggestive evidence that genetic effects are stronger during than before pregnancy. We provide an empirical example illustrating the use of these genetic variants as instruments to evaluate the effects of risk factors on birth weight. Finally, we offer suggestions for researchers contemplating the use of these variants as instruments. PMID:23701534

Etiology of depression comorbidity in combat-related PTSD: a review of the literature.

PubMed

Stander, Valerie A; Thomsen, Cynthia J; Highfill-McRoy, Robyn M

2014-03-01

Posttraumatic stress disorder is often diagnosed with other mental health problems, particularly depression. Although PTSD comorbidity has been associated with more severe and chronic symptomology, relationships among commonly co-occurring disorders are not well understood. The purpose of this study was to review the literature regarding the development of depression comorbid with combat-related PTSD among military personnel. We summarize results of commonly tested hypotheses about the etiology of PTSD and depression comorbidity, including (1) causal hypotheses, (2) common factor hypotheses, and (3) potential confounds. Evidence suggests that PTSD may be a causal risk factor for subsequent depression; however, associations are likely complex, involving bidirectional causality, common risk factors, and common vulnerabilities. The unique nature of PTSD-depression comorbidity in the context of military deployment and combat exposure is emphasized. Implications of our results for clinical practice and future research are discussed. Published by Elsevier Ltd.

Breast-feeding and cardiovascular risk factors and outcomes in later life: evidence from epidemiological studies.

PubMed

Owen, Christopher G; Whincup, Peter H; Cook, Derek G

2011-11-01

This paper considers the body of observational evidence examining the association of being breast-fed to cardiovascular risk factors and outcomes in later life, and whether any potentially advantageous findings are causal. Early cardiovascular consequences/correlates of breast-feeding, compared to being formula fed, include markedly higher levels of total blood cholesterol, lower levels of pre-prandial blood glucose and insulin and lower levels of adiposity. However, a key issue is whether these early differences at a period of rapid development programme/influence cardiovascular risk factors and outcomes in later life. Evidence of long-term effects of early feeding, largely from observational studies, has shown that those breast-fed have lower levels of blood total cholesterol, lower risk of type-2 diabetes and marginally lower levels of adiposity and blood pressure in adult life. There is no strong evidence to suggest effects of early feeding on adult levels of blood glucose, blood insulin and CHD outcomes, although further data are needed. However, the influence of confounding factors, such as maternal body size, maternal smoking and socio-demographic factors, and exclusivity of early feeding on these potentially beneficial associations needs to be considered before inferring any causal effects. Moreover, fewer studies have examined whether duration of exclusive breast-feeding has a graded influence on these risk factors and outcomes; such data would help further in deciding upon causal associations. While strong observational evidence suggests nutritional programming of adult cholesterol levels, associations with other markers of cardiometabolic risk and their consequences in later life need to be confirmed in well-conducted observational and experimental studies.

Social determinants of common metabolic risk factors (high blood pressure, high blood sugar, high body mass index and high waist-hip ratio) of major non-communicable diseases in South Asia region: a systematic review protocol.

PubMed

Sharma, Sudesh Raj; Mishra, Shiva Raj; Wagle, Kusum; Page, Rachel; Matheson, Anna; Lambrick, Danielle; Faulkner, James; Lounsbury, David; Vaidya, Abhinav

2017-09-07

Prevalence of non-communicable diseases has been increasing at a greater pace in developing countries and, in particular, the South Asia region. Various behavioral, social and environmental factors present in this region perpetuate common metabolic risk factors of non-communicable diseases. This study will identify social determinants of common metabolic risk factors of major non-communicable diseases in the context of the South Asian region and map their causal pathway. A systematic review of selected articles will be carried out following Cochrane guidelines. Review will be guided by Social Determinants of Health Framework developed by the World Health Organization to extract social determinants of metabolic risk factors of non-communicable diseases from studies. A distinct search strategy will be applied using key words to screen relevant studies from online databases. Primary and grey literature published from the year 2000 to 2016 and studies with discussion on proximal and distal determinants of non-communicable risk factors among adults of the South Asia region will be selected. They will be further checked for quality, and a matrix illustrating contents of selected articles will be developed. Thematic content analysis will be done to trace social determinants and their interaction with metabolic risk factors. Findings will be illustrated in causal loop diagrams with social determinants of risk factors along with their interaction (feedback mechanism). The review will describe the interplay of social determinants of common NCD metabolic risk factors in the form of causal loop diagram. Findings will be structured in two parts: the first part will explain the linkage between proximal determinants with the metabolic risk factors and the second part will describe the linkage among the risk factors, proximal determinants and distal determinants. Evidences across different regions will be discussed to compare and validate and/or contrast the findings. Possible bias and limitations of this study will also be discussed. PROSPERO CRD42017067212.

Identifying Causal Risk Factors for Violence among Discharged Patients

PubMed Central

Coid, Jeremy W.; Kallis, Constantinos; Doyle, Mike; Shaw, Jenny; Ullrich, Simone

2015-01-01

Background Structured Professional Judgement (SPJ) is routinely administered in mental health and criminal justice settings but cannot identify violence risk above moderate accuracy. There is no current evidence that violence can be prevented using SPJ. This may be explained by routine application of predictive instead of causal statistical models when standardising SPJ instruments. Methods We carried out a prospective cohort study of 409 male and female patients discharged from medium secure services in England and Wales to the community. Measures were taken at baseline (pre-discharge), 6 and 12 months post-discharge using the Historical, Clinical and Risk-20 items version 3 (HCR-20v3) and Structural Assessment of Protective Factors (SAPROF). Information on violence was obtained via the McArthur community violence instrument and the Police National Computer. Results In a lagged model, HCR-20v3 and SAPROF items were poor predictors of violence. Eight items of the HCR-20v3 and 4 SAPROF items did not predict violent behaviour better than chance. In re-analyses considering temporal proximity of risk/ protective factors (exposure) on violence (outcome), risk was elevated due to violent ideation (OR 6.98, 95% CI 13.85–12.65, P<0.001), instability (OR 5.41, 95% CI 3.44–8.50, P<0.001), and poor coping/ stress (OR 8.35, 95% CI 4.21–16.57, P<0.001). All 3 risk factors were explanatory variables which drove the association with violent outcome. Self-control (OR 0.13, 95% CI 0.08–0.24, P<0.001) conveyed protective effects and explained the association of other protective factors with violence. Conclusions Using two standardised SPJ instruments, predictive (lagged) methods could not identify risk and protective factors which must be targeted in interventions for discharged patients with severe mental illness. Predictive methods should be abandoned if the aim is to progress from risk assessment to effective risk management and replaced by methods which identify factors causally associated with violence. PMID:26554711

A Hierarchical Causal Taxonomy of Psychopathology across the Life Span

PubMed Central

Lahey, Benjamin B.; Krueger, Robert F.; Rathouz, Paul J.; Waldman, Irwin D.; Zald, David H.

2016-01-01

We propose a taxonomy of psychopathology based on patterns of shared causal influences identified in a review of multivariate behavior genetic studies that distinguish genetic and environmental influences that are either common to multiple dimensions of psychopathology or unique to each dimension. At the phenotypic level, first-order dimensions are defined by correlations among symptoms; correlations among first-order dimensions similarly define higher-order domains (e.g., internalizing or externalizing psychopathology). We hypothesize that the robust phenotypic correlations among first-order dimensions reflect a hierarchy of increasingly specific etiologic influences. Some nonspecific etiologic factors increase risk for all first-order dimensions of psychopathology to varying degrees through a general factor of psychopathology. Other nonspecific etiologic factors increase risk only for all first-order dimensions within a more specific higher-order domain. Furthermore, each first-order dimension has its own unique causal influences. Genetic and environmental influences common to family members tend to be nonspecific, whereas environmental influences unique to each individual are more dimension-specific. We posit that these causal influences on psychopathology are moderated by sex and developmental processes. This causal taxonomy also provides a novel framework for understanding the heterogeneity of each first-order dimension: Different persons exhibiting similar symptoms may be influenced by different combinations of etiologic influences from each of the three levels of the etiologic hierarchy. Furthermore, we relate the proposed causal taxonomy to transdimensional psychobiological processes, which also impact the heterogeneity of each psychopathology dimension. This causal taxonomy implies the need for changes in strategies for studying the etiology, psychobiology, prevention, and treatment of psychopathology. PMID:28004947

Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects?

PubMed

Kirkbride, James B; Susser, Ezra; Kundakovic, Marija; Kresovich, Jacob K; Davey Smith, George; Relton, Caroline L

2012-06-01

We posit that maternal prenatal nutrition can influence offspring schizophrenia risk via epigenetic effects. In this article, we consider evidence that prenatal nutrition is linked to epigenetic outcomes in offspring and schizophrenia in offspring, and that schizophrenia is associated with epigenetic changes. We focus upon one-carbon metabolism as a mediator of the pathway between perturbed prenatal nutrition and the subsequent risk of schizophrenia. Although post-mortem human studies demonstrate DNA methylation changes in brains of people with schizophrenia, such studies cannot establish causality. We suggest a testable hypothesis that utilizes a novel two-step Mendelian randomization approach, to test the component parts of the proposed causal pathway leading from prenatal nutritional exposure to schizophrenia. Applied here to a specific example, such an approach is applicable for wider use to strengthen causal inference of the mediating role of epigenetic factors linking exposures to health outcomes in population-based studies.

What matters most: quantifying an epidemiology of consequence

PubMed Central

Keyes, Katherine; Galea, Sandro

2015-01-01

Risk factor epidemiology has contributed to substantial public health success. In this essay, we argue, however, that the focus on risk factor epidemiology has led epidemiology to ever increasing focus on the estimation of precise causal effects of exposures on an outcome at the expense of engagement with the broader causal architecture that produces population health. To conduct an epidemiology of consequence, a systematic effort is needed to engage our science in a critical reflection both about how well and under what conditions or assumptions we can assess causal effects and also on what will truly matter most for changing population health. Such an approach changes the priorities and values of the discipline and requires reorientation of how we structure the questions we ask and the methods we use, as well as how we teach epidemiology to our emerging scholars. PMID:25749559

A hierarchical causal taxonomy of psychopathology across the life span.

PubMed

Lahey, Benjamin B; Krueger, Robert F; Rathouz, Paul J; Waldman, Irwin D; Zald, David H

2017-02-01

We propose a taxonomy of psychopathology based on patterns of shared causal influences identified in a review of multivariate behavior genetic studies that distinguish genetic and environmental influences that are either common to multiple dimensions of psychopathology or unique to each dimension. At the phenotypic level, first-order dimensions are defined by correlations among symptoms; correlations among first-order dimensions similarly define higher-order domains (e.g., internalizing or externalizing psychopathology). We hypothesize that the robust phenotypic correlations among first-order dimensions reflect a hierarchy of increasingly specific etiologic influences . Some nonspecific etiologic factors increase risk for all first-order dimensions of psychopathology to varying degrees through a general factor of psychopathology. Other nonspecific etiologic factors increase risk only for all first-order dimensions within a more specific higher-order domain. Furthermore, each first-order dimension has its own unique causal influences. Genetic and environmental influences common to family members tend to be nonspecific, whereas environmental influences unique to each individual are more dimension-specific. We posit that these causal influences on psychopathology are moderated by sex and developmental processes. This causal taxonomy also provides a novel framework for understanding the heterogeneity of each first-order dimension: Different persons exhibiting similar symptoms may be influenced by different combinations of etiologic influences from each of the 3 levels of the etiologic hierarchy. Furthermore, we relate the proposed causal taxonomy to transdimensional psychobiological processes, which also impact the heterogeneity of each psychopathology dimension. This causal taxonomy implies the need for changes in strategies for studying the etiology, psychobiology, prevention, and treatment of psychopathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Are Hill's criteria for causality satisfied for vitamin D and periodontal disease?

PubMed

Grant, William B; Boucher, Barbara J

2010-01-01

There is mounting evidence that periodontal disease (PD) is linked to low serum 25-hydroxyvitamin D [25(OH)D] concentrations in addition to recognized risk factors like diet and smoking. This paper reviews this evidence using Hill's criteria for causality in a biological system. Evidence for strength of association, consistency, cohesion and 'dose-effects' [biological 'gradients'] include strong inverse correlations between serum 25(OH) and PD cross-sectionally and that PD is consistently more prevalent in darker vs. lighter skinned people and increases at higher latitudes with analogy for gingivitis and for disorders associated with PD whose risks also increase with hypovitaminosis D. Evidence for plausibility includes that vitamin D increases calcium absorption and protects bone strength; induces formation of cathelicidin and other defensins that combat bacterial infection; reduces tissue production of destructive matrix metalloproteinases actively associated with PD and that prevalence of PD varies with common vitamin D receptor polymorphisms. Experimental evidence from limited supplementation studies [using calcium and vitamin D] shows that supplementation reduces tooth loss. Thus, existing evidence for hypovitaminosis D as a risk factor for PD to date meets Hill's criteria for causality in a biological system. Further experimental evidence for effectiveness and temporality, preferably from randomized controlled trials of vitamin D supplementation [adjusting for other PD risk factors including diet and smoking to reduce confounding] are necessary to confirm causality. If confirmed, dentists and periodontists could perform a valuable service to their patients by discussing the importance of adequate vitamin D status and how to avoid deficiency.

Are Hill's criteria for causality satisfied for vitamin D and periodontal disease?

PubMed Central

Boucher, Barbara J

2010-01-01

There is mounting evidence that periodontal disease (PD) is linked to low serum 25-hydroxyvitamin D [25(OH)D] concentrations in addition to recognized risk factors like diet and smoking. This paper reviews this evidence using Hill's criteria for causality in a biological system. Evidence for strength of association, consistency, cohesion and ‘dose-effects’ [biological ‘gradients’] include strong inverse correlations between serum 25(OH) and PD cross-sectionally and that PD is consistently more prevalent in darker vs. lighter skinned people and increases at higher latitudes with analogy for gingivitis and for disorders associated with PD whose risks also increase with hypovitaminosis D. Evidence for plausibility includes that vitamin D increases calcium absorption and protects bone strength; induces formation of cathelicidin and other defensins that combat bacterial infection; reduces tissue production of destructive matrix metalloproteinases actively associated with PD and that prevalence of PD varies with common vitamin D receptor polymorphisms. Experimental evidence from limited supplementation studies [using calcium and vitamin D] shows that supplementation reduces tooth loss. Thus, existing evidence for hypovitaminosis D as a risk factor for PD to date meets Hill's criteria for causality in a biological system. Further experimental evidence for effectiveness and temporality, preferably from randomized controlled trials of vitamin D supplementation [adjusting for other PD risk factors including diet and smoking to reduce confounding] are necessary to confirm causality. If confirmed, dentists and periodontists could perform a valuable service to their patients by discussing the importance of adequate vitamin D status and how to avoid deficiency. PMID:21547146

What matters most: quantifying an epidemiology of consequence.

PubMed

Keyes, Katherine; Galea, Sandro

2015-05-01

Risk factor epidemiology has contributed to substantial public health success. In this essay, we argue, however, that the focus on risk factor epidemiology has led epidemiology to ever increasing focus on the estimation of precise causal effects of exposures on an outcome at the expense of engagement with the broader causal architecture that produces population health. To conduct an epidemiology of consequence, a systematic effort is needed to engage our science in a critical reflection both about how well and under what conditions or assumptions we can assess causal effects and also on what will truly matter most for changing population health. Such an approach changes the priorities and values of the discipline and requires reorientation of how we structure the questions we ask and the methods we use, as well as how we teach epidemiology to our emerging scholars. Copyright © 2015 Elsevier Inc. All rights reserved.

Improved classification of evidence for EMF health risks.

PubMed

Leitgeb, Norbert

2012-08-01

Classifying evidence of causality between a risk factor and its potential health effect is challenging, in particular in an already emotional situation. Even the assessment of health risks by designated bodies may still depend on their composition of individuals with their background, bias, and, in worst case, their interests. This may explain opposing conclusions from the same pool of data which, consequently, may undermine credibility if not communicated properly. To overcome existing weakness in classifying and communicating evidence of health risks such as from electromagnetic fields, a new rule-based approach is presented. Developed by the German Commission on Radiological Protection (SSK), it discloses step-by-step the criteria for weighing scientific data and pools partial evidences of different scientific approaches to conclude on the overall evidence of causality between risk factor and effects. The validity of the approach is demonstrated by analyzing evidence of carcinogenicity of ionizing radiation, mobile phone use, and nocturnal exposure to visible light.

"Fundamental Causes" of Social Inequalities in Mortality: A Test of the Theory

ERIC Educational Resources Information Center

Phelan, Jo C.; Link, Bruce G.; Diez-Roux, Ana; Kawachi, Ichiro; Levin, Bruce

2004-01-01

Medicine and epidemiology currently dominate the study of the strong association between socioeconomic status and mortality. Socioeconomic status typically is viewed as a causally irrelevant "confounding variable" or as a less critical variable marking only the beginning of a causal chain in which intervening risk factors are given prominence. Yet…

Prediction versus aetiology: common pitfalls and how to avoid them.

PubMed

van Diepen, Merel; Ramspek, Chava L; Jager, Kitty J; Zoccali, Carmine; Dekker, Friedo W

2017-04-01

Prediction research is a distinct field of epidemiologic research, which should be clearly separated from aetiological research. Both prediction and aetiology make use of multivariable modelling, but the underlying research aim and interpretation of results are very different. Aetiology aims at uncovering the causal effect of a specific risk factor on an outcome, adjusting for confounding factors that are selected based on pre-existing knowledge of causal relations. In contrast, prediction aims at accurately predicting the risk of an outcome using multiple predictors collectively, where the final prediction model is usually based on statistically significant, but not necessarily causal, associations in the data at hand.In both scientific and clinical practice, however, the two are often confused, resulting in poor-quality publications with limited interpretability and applicability. A major problem is the frequently encountered aetiological interpretation of prediction results, where individual variables in a prediction model are attributed causal meaning. This article stresses the differences in use and interpretation of aetiological and prediction studies, and gives examples of common pitfalls. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Beliefs and perceptions about the causes of breast cancer: a case-control study.

PubMed

Thomson, Allyson K; Heyworth, Jane S; Girschik, Jennifer; Slevin, Terry; Saunders, Christobel; Fritschi, Lin

2014-08-21

Attributions of causality are common for many diseases, including breast cancer. The risk of developing breast cancer can be reduced by modifications to lifestyle and behaviours to minimise exposure to specific risk factors, such as obesity. However, these modifications will only occur if women believe that certain behaviours/lifestyle factors have an impact on the development of breast cancer. The Breast Cancer, Environment and Employment Study is a case-control study of breast cancer conducted in Western Australia between 2009 and 2011. As part of the study 1109 women with breast cancer and 1633 women without the disease completed a Risk Perception Questionnaire in which they were asked in an open-ended question for specific cause/s to the development of breast cancer in themselves or in others. The study identified specific causal beliefs, and assessed differences in the beliefs between women with and without breast cancer. The most common attributions in women without breast cancer were to familial or inherited factors (77.6%), followed by lifestyle factors, such as poor diet and smoking (47.1%), and environmental factors, such as food additives (45.4%). The most common attributions in women with breast cancer were to mental or emotional factors (46.3%), especially stress, followed by lifestyle factors (38.6%) and physiological factors (37.5%), particularly relating to hormonal history. While the majority of participants in this study provided one or more causal attributions for breast cancer, many of the reported risk factors do not correspond to those generally accepted by the scientific community. These misperceptions could be having a significant impact on the success of prevention and early detection programs that seek to minimise the pain and suffering caused by this disease. In particular, women who have no family history of the disease may not work to minimise their exposure to the modifiable risk factors.

Underweight as a risk factor for respiratory death in the Whitehall cohort study: exploring reverse causality using a 45-year follow-up.

PubMed

Kivimäki, Mika; Shipley, Martin J; Bell, Joshua A; Brunner, Eric J; Batty, G David; Singh-Manoux, Archana

2016-01-01

Underweight adults have higher rates of respiratory death than the normal weight but it is unclear whether this association is causal or reflects illness-induced weight loss (reverse causality). Evidence from a 45-year follow-up of underweight participants for respiratory mortality in the Whitehall study (N=18 823; 2139 respiratory deaths) suggests that excess risk among the underweight is attributable to reverse causality. The age-adjusted and smoking-adjusted risk was 1.55-fold (95% CI 1.32 to 1.83) higher among underweight compared with normal weight participants, but attenuated in a stepwise manner to 1.14 (95% CI 0.76 to 1.71) after serial exclusions of deaths during the first 5-35 years of follow-up (P(trend)<0.001). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A genetically informative developmental study of the relationship between conduct disorder and peer deviance in males

PubMed Central

Kendler, K. S.; Jacobson, K.; Myers, J. M.; Eaves, L. J.

2014-01-01

Background Conduct disorder (CD) and peer deviance (PD) both powerfully predict future externalizing behaviors. Although levels of CD and PD are strongly correlated, the causal relationship between them has remained controversial and has not been examined by a genetically informative study. Method Levels of CD and PD were assessed in 746 adult male–male twin pairs at personal interview for ages 8–11, 12–14 and 15–17 years using a life history calendar. Model fitting was performed using the Mx program. Results The best-fit model indicated an active developmental relationship between CD and PD including forward transmission of both traits over time and strong causal relationships between CD and PD within time periods. The best-fit model indicated that the causal relationship for genetic risk factors was from CD to PD and was constant over time. For common environmental factors, the causal pathways ran from PD to CD and were stronger in earlier than later age periods. Conclusions A genetically informative model revealed causal pathways difficult to elucidate by other methods. Genes influence risk for CD, which, through social selection, impacts on the deviance of peers. Shared environment, through family and community processes, encourages or discourages adolescent deviant behavior, which, via social influence, alters risk for CD. Social influence is more important than social selection in childhood, but by late adolescence social selection becomes predominant. These findings have implications for prevention efforts for CD and associated externalizing disorders. PMID:17935643

Approaches for Strengthening Causal Inference Regarding Prenatal Risk Factors for Childhood Behavioural and Psychiatric Disorders

ERIC Educational Resources Information Center

Lewis, Sarah J.; Relton, Caroline; Zammit, Stanley; Smith, George Davey

2013-01-01

Background: The risk of childhood behavioural and psychiatric diseases could be substantially reduced if modifiable risk factors for these disorders were identified. The critical period for many of these exposures is likely to be in utero as this is the time when brain development is most rapid. However, due to confounding and other limitations of…

Smoking and multiple sclerosis: A systematic review and meta-analysis using the Bradford Hill criteria for causation.

PubMed

Degelman, Michelle L; Herman, Katya M

2017-10-01

Despite being one of the most common neurological disorders globally, the cause(s) of multiple sclerosis (MS) remain unknown. Cigarette smoking has been studied with regards to both the development and progression of MS. The Bradford Hill criteria for causation can contribute to a more comprehensive evaluation of a potentially causal risk factor-disease outcome relationship. The objective of this systematic review and meta-analysis was to assess the relationship between smoking and both MS risk and MS progression, subsequently applying Hill's criteria to further evaluate the likelihood of causal associations. The Medline, EMBASE, CINAHL, PsycInfo, and Cochrane Library databases were searched for relevant studies up until July 28, 2015. A random-effects meta-analysis was conducted for three outcomes: MS risk, conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS), and progression from relapsing-remitting multiple sclerosis (RRMS) to secondary-progressive multiple sclerosis (SPMS). Dose-response relationships and risk factor interactions, and discussions of mechanisms and analogous associations were noted. Hill's criteria were applied to assess causality of the relationships between smoking and each outcome. The effect of second-hand smoke exposure was also briefly reviewed. Smoking had a statistically significant association with both MS risk (conservative: OR/RR 1.54, 95% CI [1.46-1.63]) and SPMS risk (HR 1.80, 95% CI [1.04-3.10]), but the association with progression from CIS to CDMS was non-significant (HR 1.13, 95% CI [0.73-1.76]). Using Hill's criteria, there was strong evidence of a causal role of smoking in MS risk, but only moderate evidence of a causal association between smoking and MS progression. Heterogeneity in study designs and target populations, inconsistent results, and an overall scarcity of studies point to the need for more research on second-hand smoke exposure in relation to MS prior to conducting a detailed meta-analysis. This first review to supplement systematic review and meta-analytic methods with Hill's criteria to analyze the smoking-MS association provides evidence supporting the causal involvement of smoking in the development and progression of MS. Smoking prevention and cessation programs and policies should consider MS as an additional health risk when aiming to reduce smoking prevalence in the population. Copyright © 2017 Elsevier B.V. All rights reserved.

STAMP-Based HRA Considering Causality Within a Sociotechnical System: A Case of Minuteman III Missile Accident.

PubMed

Rong, Hao; Tian, Jin

2015-05-01

The study contributes to human reliability analysis (HRA) by proposing a method that focuses more on human error causality within a sociotechnical system, illustrating its rationality and feasibility by using a case of the Minuteman (MM) III missile accident. Due to the complexity and dynamics within a sociotechnical system, previous analyses of accidents involving human and organizational factors clearly demonstrated that the methods using a sequential accident model are inadequate to analyze human error within a sociotechnical system. System-theoretic accident model and processes (STAMP) was used to develop a universal framework of human error causal analysis. To elaborate the causal relationships and demonstrate the dynamics of human error, system dynamics (SD) modeling was conducted based on the framework. A total of 41 contributing factors, categorized into four types of human error, were identified through the STAMP-based analysis. All factors are related to a broad view of sociotechnical systems, and more comprehensive than the causation presented in the accident investigation report issued officially. Recommendations regarding both technical and managerial improvement for a lower risk of the accident are proposed. The interests of an interdisciplinary approach provide complementary support between system safety and human factors. The integrated method based on STAMP and SD model contributes to HRA effectively. The proposed method will be beneficial to HRA, risk assessment, and control of the MM III operating process, as well as other sociotechnical systems. © 2014, Human Factors and Ergonomics Society.

Development and Coherence of Beliefs Regarding Disease Causality and Prevention

ERIC Educational Resources Information Center

Sigelman, Carol K.

2014-01-01

Guided by a naïve theories perspective on the development of thinking about disease, this study of 188 children aged 6 to 18 examined knowledge of HIV/AIDS causality and prevention using parallel measures derived from open-ended and structured interviews. Knowledge of both risk factors and prevention rules, as well as conceptual understanding of…

Modelling cointegration and Granger causality network to detect long-term equilibrium and diffusion paths in the financial system.

PubMed

Gao, Xiangyun; Huang, Shupei; Sun, Xiaoqi; Hao, Xiaoqing; An, Feng

2018-03-01

Microscopic factors are the basis of macroscopic phenomena. We proposed a network analysis paradigm to study the macroscopic financial system from a microstructure perspective. We built the cointegration network model and the Granger causality network model based on econometrics and complex network theory and chose stock price time series of the real estate industry and its upstream and downstream industries as empirical sample data. Then, we analysed the cointegration network for understanding the steady long-term equilibrium relationships and analysed the Granger causality network for identifying the diffusion paths of the potential risks in the system. The results showed that the influence from a few key stocks can spread conveniently in the system. The cointegration network and Granger causality network are helpful to detect the diffusion path between the industries. We can also identify and intervene in the transmission medium to curb risk diffusion.

Modelling cointegration and Granger causality network to detect long-term equilibrium and diffusion paths in the financial system

PubMed Central

Huang, Shupei; Sun, Xiaoqi; Hao, Xiaoqing; An, Feng

2018-01-01

Microscopic factors are the basis of macroscopic phenomena. We proposed a network analysis paradigm to study the macroscopic financial system from a microstructure perspective. We built the cointegration network model and the Granger causality network model based on econometrics and complex network theory and chose stock price time series of the real estate industry and its upstream and downstream industries as empirical sample data. Then, we analysed the cointegration network for understanding the steady long-term equilibrium relationships and analysed the Granger causality network for identifying the diffusion paths of the potential risks in the system. The results showed that the influence from a few key stocks can spread conveniently in the system. The cointegration network and Granger causality network are helpful to detect the diffusion path between the industries. We can also identify and intervene in the transmission medium to curb risk diffusion. PMID:29657804

Mendelian randomisation implicates hyperlipidaemia as a risk factor for colorectal cancer.

PubMed

Rodriguez-Broadbent, Henry; Law, Philip J; Sud, Amit; Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hänninen, Ulrika A; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Sarin, Antti-Pekka; Ripatti, Samuli; Eriksson, Johan G; Rissanen, Harri; Knekt, Paul; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Palotie, Aarno; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Martin, Lynn; Barclay, Ella; Farrington, Susan M; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Timothy S; Kaplan, Richard; Kerr, Rachel; Kerr, David; Passarelli, Michael N; Figueiredo, Jane C; Buchanan, Daniel D; Win, Aung K; Hopper, John L; Jenkins, Mark A; Lindor, Noralane M; Newcomb, Polly A; Gallinger, Steven; Conti, David; Schumacher, Fred; Casey, Graham; Aaltonen, Lauri A; Cheadle, Jeremy P; Tomlinson, Ian P; Dunlop, Malcolm G; Houlston, Richard S

2017-06-15

While elevated blood cholesterol has been associated with an increased risk of colorectal cancer (CRC) in observational studies, causality is uncertain. Here we apply a Mendelian randomisation (MR) analysis to examine the potential causal relationship between lipid traits and CRC risk. We used single nucleotide polymorphisms (SNPs) associated with blood levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as instrumental variables (IV). We calculated MR estimates for each risk factor with CRC using SNP-CRC associations from 9,254 cases and 18,386 controls. Genetically predicted higher TC was associated with an elevated risk of CRC (odds ratios (OR) per unit SD increase = 1.46, 95% confidence interval [CI]: 1.20-1.79, p = 1.68 × 10 -4 ). The pooled ORs for LDL, HDL, and TG were 1.05 (95% CI: 0.92-1.18, p = 0.49), 0.94 (95% CI: 0.84-1.05, p = 0.27), and 0.98 (95% CI: 0.85-1.12, p = 0.75) respectively. A genetic risk score for 3-hydoxy-3-methylglutaryl-coenzyme A reductase (HMGCR) to mimic the effects of statin therapy was associated with a reduced CRC risk (OR = 0.69, 95% CI: 0.49-0.99, p = 0.046). This study supports a causal relationship between higher levels of TC with CRC risk, and a further rationale for implementing public health strategies to reduce the prevalence of hyperlipidaemia. © 2017 UICC.

Statistical Evidence Suggests that Inattention Drives Hyperactivity/Impulsivity in Attention Deficit-Hyperactivity Disorder

PubMed Central

Sokolova, Elena; Groot, Perry; Claassen, Tom; van Hulzen, Kimm J.; Glennon, Jeffrey C.; Franke, Barbara

2016-01-01

Background Numerous factor analytic studies consistently support a distinction between two symptom domains of attention-deficit/hyperactivity disorder (ADHD), inattention and hyperactivity/impulsivity. Both dimensions show high internal consistency and moderate to strong correlations with each other. However, it is not clear what drives this strong correlation. The aim of this paper is to address this issue. Method We applied a sophisticated approach for causal discovery on three independent data sets of scores of the two ADHD dimensions in NeuroIMAGE (total N = 675), ADHD-200 (N = 245), and IMpACT (N = 164), assessed by different raters and instruments, and further used information on gender or a genetic risk haplotype. Results In all data sets we found strong statistical evidence for the same pattern: the clear dependence between hyperactivity/impulsivity symptom level and an established genetic factor (either gender or risk haplotype) vanishes when one conditions upon inattention symptom level. Under reasonable assumptions, e.g., that phenotypes do not cause genotypes, a causal model that is consistent with this pattern contains a causal path from inattention to hyperactivity/impulsivity. Conclusions The robust dependency cancellation observed in three different data sets suggests that inattention is a driving factor for hyperactivity/impulsivity. This causal hypothesis can be further validated in intervention studies. Our model suggests that interventions that affect inattention will also have an effect on the level of hyperactivity/impulsivity. On the other hand, interventions that affect hyperactivity/impulsivity would not change the level of inattention. This causal model may explain earlier findings on heritable factors causing ADHD reported in the study of twins with learning difficulties. PMID:27768717

Critical factors and paths influencing construction workers' safety risk tolerances.

PubMed

Wang, Jiayuan; Zou, Patrick X W; Li, Penny P

2016-08-01

While workers' safety risk tolerances have been regarded as a main reason for their unsafe behaviors, little is known about why different people have different risk tolerances even when confronting the same situation. The aim of this research is to identify the critical factors and paths that influence workers' safety risk tolerance and to explore how they contribute to accident causal model from a system thinking perceptive. A number of methods were carried out to analyze the data collected through interviews and questionnaire surveys. In the first and second steps of the research, factor identification, factor ranking and factor analysis were carried out, and the results show that workers' safety risk tolerance can be influenced by four groups of factors, namely: (1) personal subjective perception; (2) work knowledge and experiences; (3) work characteristics; and (4) safety management. In the third step of the research, hypothetical influencing path model was developed and tested by using structural equation modeling (SEM). It is found that the effects of external factors (safety management and work characteristics) on risk tolerance are larger than that of internal factors (personal subjective perception and work knowledge & experiences). Specifically, safety management contributes the most to workers' safety risk tolerance through its direct effect and indirect effect; while personal subjective perception comes the second and can act as an intermedia for work characteristics. This research provides an in-depth insight of workers' unsafe behaviors by depicting the contributing factors as shown in the accident causal model developed in this research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Post-traumatic stress disorder and cardiometabolic disease: improving causal inference to inform practice.

PubMed

Koenen, K C; Sumner, J A; Gilsanz, P; Glymour, M M; Ratanatharathorn, A; Rimm, E B; Roberts, A L; Winning, A; Kubzansky, L D

2017-01-01

Post-traumatic stress disorder (PTSD) has been declared 'a life sentence' based on evidence that the disorder leads to a host of physical health problems. Some of the strongest empirical research - in terms of methodology and findings - has shown that PTSD predicts higher risk of cardiometabolic diseases, specifically cardiovascular disease (CVD) and type 2 diabetes (T2D). Despite mounting evidence, PTSD is not currently acknowledged as a risk factor by cardiovascular or endocrinological medicine. This view is unlikely to change absent compelling evidence that PTSD causally contributes to cardiometabolic disease. This review suggests that with developments in methods for epidemiological research and the rapidly expanding knowledge of the behavioral and biological effects of PTSD the field is poised to provide more definitive answers to questions of causality. First, we discuss methods to improve causal inference using the observational data most often used in studies of PTSD and health, with particular reference to issues of temporality and confounding. Second, we consider recent work linking PTSD with specific behaviors and biological processes, and evaluate whether these may plausibly serve as mechanisms by which PTSD leads to cardiometabolic disease. Third, we evaluate how looking more comprehensively into the PTSD phenotype provides insight into whether specific aspects of PTSD phenomenology are particularly relevant to cardiometabolic disease. Finally, we discuss new areas of research that are feasible and could enhance understanding of the PTSD-cardiometabolic relationship, such as testing whether treatment of PTSD can halt or even reverse the cardiometabolic risk factors causally related to CVD and T2D.

The burden of cancer attributable to modifiable risk factors: the Australian cancer-PAF cohort consortium.

PubMed

Arriaga, Maria E; Vajdic, Claire M; Canfell, Karen; MacInnis, Robert; Hull, Peter; Magliano, Dianna J; Banks, Emily; Giles, Graham G; Cumming, Robert G; Byles, Julie E; Taylor, Anne W; Shaw, Jonathan E; Price, Kay; Hirani, Vasant; Mitchell, Paul; Adelstein, Barbara-Ann; Laaksonen, Maarit A

2017-06-14

To estimate the Australian cancer burden attributable to lifestyle-related risk factors and their combinations using a novel population attributable fraction (PAF) method that accounts for competing risk of death, risk factor interdependence and statistical uncertainty. 365 173 adults from seven Australian cohort studies. We linked pooled harmonised individual participant cohort data with population-based cancer and death registries to estimate exposure-cancer and exposure-death associations. Current Australian exposure prevalence was estimated from representative external sources. To illustrate the utility of the new PAF method, we calculated fractions of cancers causally related to body fatness or both tobacco and alcohol consumption avoidable in the next 10 years by risk factor modifications, comparing them with fractions produced by traditional PAF methods. Over 10 years of follow-up, we observed 27 483 incident cancers and 22 078 deaths. Of cancers related to body fatness (n=9258), 13% (95% CI 11% to 16%) could be avoided if those currently overweight or obese had body mass index of 18.5-24.9 kg/m 2 . Of cancers causally related to both tobacco and alcohol (n=4283), current or former smoking explains 13% (11% to 16%) and consuming more than two alcoholic drinks per day explains 6% (5% to 8%). The two factors combined explain 16% (13% to 19%): 26% (21% to 30%) in men and 8% (4% to 11%) in women. Corresponding estimates using the traditional PAF method were 20%, 31% and 10%. Our PAF estimates translate to 74 000 avoidable body fatness-related cancers and 40 000 avoidable tobacco- and alcohol-related cancers in Australia over the next 10 years (2017-2026). Traditional PAF methods not accounting for competing risk of death and interdependence of risk factors may overestimate PAFs and avoidable cancers. We will rank the most important causal factors and their combinations for a spectrum of cancers and inform cancer control activities. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Academic Risk Factors and Deficits of Learned Hopelessness: A Longitudinal Study of Hong Kong Secondary School Students

ERIC Educational Resources Information Center

Au, Raymond C. P.; Watkins, David A.; Hattie, John A. C.

2010-01-01

The aim of the present study is to explore a causal model of academic achievement and learning-related personal variables by testing the nature of relationships between learned hopelessness, its risk factors and hopelessness deficits as proposed in major theories in this area. The model investigates affective-motivational characteristics of…

Causal inference in public health.

PubMed

Glass, Thomas A; Goodman, Steven N; Hernán, Miguel A; Samet, Jonathan M

2013-01-01

Causal inference has a central role in public health; the determination that an association is causal indicates the possibility for intervention. We review and comment on the long-used guidelines for interpreting evidence as supporting a causal association and contrast them with the potential outcomes framework that encourages thinking in terms of causes that are interventions. We argue that in public health this framework is more suitable, providing an estimate of an action's consequences rather than the less precise notion of a risk factor's causal effect. A variety of modern statistical methods adopt this approach. When an intervention cannot be specified, causal relations can still exist, but how to intervene to change the outcome will be unclear. In application, the often-complex structure of causal processes needs to be acknowledged and appropriate data collected to study them. These newer approaches need to be brought to bear on the increasingly complex public health challenges of our globalized world.

A review of caffeine use as a risk or protective factor for women's health and pregnancy.

PubMed

Peacock, Amy; Mattick, Richard P; Bruno, Raimondo

2017-07-01

To provide a narrative synthesis of recently published studies on caffeine use as a risk or protective factor for health outcomes, with a focus on women's health and pregnancy. Based on predominantly observational studies, moderate caffeine intake has been shown to be a protective factor for liver cancer, certain bowel conditions, colorectal cancer, skin cancer, and regular menstrual cycle function. However, heavy consumption is a risk factor for osteoporosis, urinary incontinence, and poorer birth and child developmental outcomes. Residual confounding and issues surrounding retrospective self-reported intake are cited as key limitations in the majority of these studies. Moderate caffeine intake has been associated with lower risk of cardiovascular disease and metabolic syndrome; however, recent genetic epidemiology studies provide no evidence for a causal relationship. Greater inclusion of female participants in studies, and analysis of sex differences in the relationship between caffeine intake and certain health conditions, is necessary. The current literature suggests caffeine's role as a risk or protective factor differs across health conditions. Often, there are plausible biological mechanisms for this relationship. However, a continued precautionary stance is recommended until direct causal pathways are established. Review of recently published studies does not suggest that current intake guidelines for adults and for pregnant woman need to be modified.

Occupational Factors, Fatigue, and Cardiovascular Disease

PubMed Central

2009-01-01

Purpose: Briefly identify the epidemiological evidence, propose pertinent mechanisms, and discuss physical therapy practice as well as research implications of a causal association between occupational factors and cardiovascular disease. Summary of Key Points: There is evidence that occupational metabolic demands and work organizations characterized by reduced worker control are associated with increased risk of cardiovascular disease. It is biologically plausible that these two factors interact to create a preclinical, intermediate state of fatigue (burnout) that is a critical component in the causal path from occupational factors to CVD. Physical therapists are uniquely qualified to contribute to an understanding of these mechanisms and their resultant implications for work organization, rehabilitation, and health promotion. Statement of Recommendations: Physical therapists engaged in ergonomic job analysis should consider work related metabolic demands, worker control, and fatigue in their assessment of risk for injury and illness, in recommendations for return to work, and in the prescription of health promotion leisure time physical activity PMID:20467535

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.

PubMed

Patel, Zubin; Lu, Xiaoming; Miller, Daniel; Forney, Carmy R; Lee, Joshua; Lynch, Arthur; Schroeder, Connor; Parks, Lois; Magnusen, Albert F; Chen, Xiaoting; Pujato, Mario; Maddox, Avery; Zoller, Erin E; Namjou, Bahram; Brunner, Hermine I; Henrickson, Michael; Huggins, Jennifer L; Williams, Adrienne H; Ziegler, Julie T; Comeau, Mary E; Marion, Miranda C; Glenn, Stuart B; Adler, Adam; Shen, Nan; Nath, Swapan K; Stevens, Anne M; Freedman, Barry I; Pons-Estel, Bernardo A; Tsao, Betty P; Jacob, Chaim O; Kamen, Diane L; Brown, Elizabeth E; Gilkeson, Gary S; Alarcón, Graciela S; Martin, Javier; Reveille, John D; Anaya, Juan-Manuel; James, Judith A; Sivils, Kathy L; Criswell, Lindsey A; Vilá, Luis M; Petri, Michelle; Scofield, R Hal; Kimberly, Robert P; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Bang, So-Young; Lee, Hye-Soon; Bae, Sang-Cheol; Boackle, Susan A; Cunninghame Graham, Deborah; Vyse, Timothy J; Merrill, Joan T; Niewold, Timothy B; Ainsworth, Hannah C; Silverman, Earl D; Weisman, Michael H; Wallace, Daniel J; Raj, Prithvi; Guthridge, Joel M; Gaffney, Patrick M; Kelly, Jennifer A; Alarcón-Riquelme, Marta E; Langefeld, Carl D; Wakeland, Edward K; Kaufman, Kenneth M; Weirauch, Matthew T; Harley, John B; Kottyan, Leah C

2018-04-18

Systemic Lupus Erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly-replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared to the non-risk allele of rs11889341. We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1.

Genetics: Implications for Prevention and Management of Coronary Artery Disease.

PubMed

Assimes, Themistocles L; Roberts, Robert

2016-12-27

An exciting new era has dawned for the prevention and management of coronary artery disease (CAD) utilizing genetic risk variants. The recent identification of over 60 susceptibility loci for CAD confirms not only the importance of established risk factors, but also the existence of many novel causal pathways that are expected to improve our understanding of the genetic basis of CAD and facilitate the development of new therapeutic agents over time. Concurrently, Mendelian randomization studies have provided intriguing insights on the causal relationship between CAD-related traits, and highlight the potential benefits of long-term modifications of risk factors. Last, genetic risk scores of CAD may serve not only as prognostic, but also as predictive markers, and carry the potential to considerably improve the delivery of established prevention strategies. This review will summarize the evolution and discovery of genetic risk variants for CAD and their current and future clinical applications. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Association of timing of menarche with depressive symptoms and depression in adolescence: Mendelian randomisation study

PubMed Central

Sequeira, Maija-Eliina; Lewis, Sarah J.; Bonilla, Carolina; Smith, George Davey; Joinson, Carol

2017-01-01

Background Observational studies report associations between early menarche and higher levels of depressive symptoms and depression. However, no studies have investigated whether this association is causal. Aims To determine whether earlier menarche is a causal risk factor for depressive symptoms and depression in adolescence. Method The associations between a genetic score for age at menarche and depressive symptoms at 14, 17 and 19 years, and depression at 18 years, were examined using Mendelian randomisation analysis techniques. Results Using a genetic risk score to indicate earlier timing of menarche, we found that early menarche is associated with higher levels of depressive symptoms at 14 years (odds ratio per risk allele 1.02, 95% CI 1.005–1.04, n = 2404). We did not find an association between the early menarche risk score and depressive symptoms or depression after age 14. Conclusions Our results provide evidence for a causal effect of age at menarche on depressive symptoms at age 14. PMID:27491534

Identification of risk factors associated with onset and progression of amyotrophic lateral sclerosis using systematic review and meta-analysis.

PubMed

Wang, Ming-Dong; Little, Julian; Gomes, James; Cashman, Neil R; Krewski, Daniel

2017-07-01

Although amyotrophic lateral sclerosis (ALS) was identified as a neurological condition 150 years ago, risk factors related to the onset and progression of ALS remain largely unknown. Monogenic mutations in over 30 genes are associated with about 10% of ALS cases. The age at onset of ALS and disease types has been found to influence ALS progression. The present study was designed to identify additional putative risk factors associated with the onset and progression of ALS using systematic review and meta-analysis of observational studies. Risk factors that may be associated with ALS include: 1) genetic mutations, including the intermediate CAG repeat expansion in ATXN2; 2) previous exposure to heavy metals such as lead and mercury; 3) previous exposure to organic chemicals, such as pesticides and solvents; 4) history of electric shock; 5) history of physical trauma/injury (including head trauma/injury); 6) smoking (a weak risk factor for ALS in women); and 6) other risk factors, such as participating in professional sports, lower body mass index, lower educational attainment, or occupations requiring repetitive/strenuous work, military service, exposure to Beta-N-methylamino-l-alanin and viral infections. Risk factors that may be associated with ALS progression rate include: 1) nutritional status, including vitamin D deficiency; 2) comorbidities; 3) ethnicity and genetic factors; 4) lack of supportive care; and 4) smoking. The extent to which these associations may be causal is discussed, with further research recommended to strengthen the evidence on which determinations of causality may be based. Copyright © 2016. Published by Elsevier B.V.

Prenatal Risk Factors and the Etiology of ADHD-Review of Existing Evidence.

PubMed

Sciberras, Emma; Mulraney, Melissa; Silva, Desiree; Coghill, David

2017-01-01

While it is well accepted that attention-deficit/hyperactivity disorder (ADHD) is a highly heritable disorder, not all of the risk is genetic. It is estimated that between 10 and 40% of the variance associated with ADHD is likely to be accounted for by environmental factors. There is considerable interest in the role that the prenatal environment might play in the development of ADHD with previous reviews concluding that despite demonstration of associations between prenatal risk factors (e.g. prematurity, maternal smoking during pregnancy) and ADHD, there remains insufficient evidence to support a definite causal relationship. This article provides an update of research investigating the relationship between prenatal risk factors and ADHD published over the past 3 years. Recently, several epidemiological and data linkage studies have made substantial contributions to our understanding of this relationship. In particular, these studies have started to account for some of the genetic and familial confounds that, when taken into account, throw several established findings into doubt. None of the proposed prenatal risk factors can be confirmed as causal for ADHD, and the stronger the study design, the less likely it is to support an association. We need a new benchmark for studies investigating the etiology of ADHD whereby there is an expectation not only that data will be collected prospectively but also that the design allows the broad range of genetic and familial factors to be accounted for.

Bilirubin as a potential causal factor in type 2 diabetes risk: a Mendelian randomization study

PubMed Central

Abbasi, Ali; Deetman, Petronella E.; Corpeleijn, Eva; Gansevoort, Ron T.; Gans, Rijk O.B.; Hillege, Hans L.; van der Harst, Pim; Stolk, Ronald P.; Navis, Gerjan; Alizadeh, Behrooz Z.; Bakker, Stephan J.L.

2014-01-01

Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (aged 28-75 years; women, 52.6%). We used rs6742078 located in UDP-glucuronosyltransferase (UGT1A1) locus as instrumental variable (IV) to study a potential causal effect of serum total bilirubin on T2D risk. T2D developed in a total of 210 (6.2%) participants during a median follow-up of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; P<1×10−122) and was also associated with T2D risk (OR 0.69 [95%CI, 0.54-0.90]; P=0.006). Per 1-SD increase in log-transformed bilirubin levels, we observed a 25% (OR 0.75 [95%CI, 0.62-0.92]; P=0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal ORIVestimation per 1-SD increase in log-transformed bilirubin 0.58 [95%CI, 0.39-0.84]; P=0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman chi-square test Pfor difference =0.19). These novel results provide evidence that elevated bilirubin is causally associated with risk of T2D and support its role as a protective determinant. PMID:25368098

[Urinary incontinence as a risk factor for pressure sores does not withstand a critical examination].

PubMed

Krause, Tom; Anders, Jennifer; von Renteln-Kruse, Wolfgang

2005-10-01

The association between urinary incontinence and pressure sores is put down to various causes. Most frequently urinary wet and following maceration of the skin are mentioned. However, it is possible that urinary incontinence is only an indicator for other risk factors or a measure of the need for care without any causal relation to pressure sores. There are hardly any controlled or randomised studies; this lack of scientific evidence is problematic. Based on a case-control-study including data of 200 patients as well as on the existing models of explanation, the following study tries to examine critically the connections between pressure sores and urinary incontinence. Out of the patients in our study population 97.5 percent were incontinent. Different categories of the risk factor urinary incontinence and different dichotomisations have led to different statistical results. Statements concerning the connection between urinary incontinence and pressure sores have to be interpreted critically. The dependence of urinary incontinence on other risk factors such as patients' need for care or compliance suggests that the causal connection to pressure sores be not reduced to the influence of wetness. We advise to research connections between urinary incontinence and pressure sores in a methodologically appropriate setting.

Developmental Dyslexia: Predicting Individual Risk

ERIC Educational Resources Information Center

Thompson, Paul A.; Hulme, Charles; Nash, Hannah M.; Gooch, Debbie; Hayiou-Thomas, Emma; Snowling, Margaret J.

2015-01-01

Background: Causal theories of dyslexia suggest that it is a heritable disorder, which is the outcome of multiple risk factors. However, whether early screening for dyslexia is viable is not yet known. Methods: The study followed children at high risk of dyslexia from preschool through the early primary years assessing them from age 3 years and 6…

Role of visceral adipose tissue in aging.

PubMed

Huffman, Derek M; Barzilai, Nir

2009-10-01

Visceral fat (VF) accretion is a hallmark of aging in humans. Epidemiologic studies have implicated abdominal obesity as a major risk factor for insulin resistance, type 2 diabetes, cardiovascular disease, metabolic syndrome and death. Studies utilizing novel rodent models of visceral obesity and surgical strategies in humans have been undertaken to determine if subcutaneous (SC) abdominal or VF are causally linked to age-related diseases. Specific depletion or expansion of the VF depot using genetic or surgical tools in rodents has been shown to have direct effects on disease risk. In contrast, surgically removing large quantities of SC fat does not consistently improve metabolic parameters in humans or rodents, while benefits were observed with SC fat expansion in mice, suggesting that SC fat accrual is not an important contributor to metabolic decline. There is also compelling evidence in humans that abdominal obesity is a stronger risk factor for mortality risk than general obesity. Likewise, we have shown that surgical removal of VF improves mean and maximum lifespan in rats, providing the first causal evidence that VF depletion may be an important underlying cause of improved lifespan with caloric restriction. This review provides both corollary and causal evidence for the importance of accounting for body fat distribution, and specifically VF, when assessing disease and mortality risk. Given the hazards of VF accumulation on health, treatment strategies aimed at selectively depleting VF should be considered as a viable tool to effectively reduce disease risk in humans.

Breast cancer: critical data analysis concludes that estrogens are not the cause, however lifestyle changes can alter risk rapidly.

PubMed

Wiseman, Richard A

2004-08-01

The theory that estrogens are causally associated with increased risk of breast cancer and the question of whether lifetime cumulative exposure is necessary are critically reviewed. Systematic search was made of published epidemiological and clinical data relating to estrogen concentrations at different times and situations, and of breast cancer incidence with age and after lifestyle changes. Breast cancer incidence increases with age, although the rate of increase slows. Reproductive factors are known to affect risk, but data that do not fit the theory of estrogen causation include low estradiol levels and decline of estrogen excretion postmenopausally, rates in HRT-takers, absence of increased rate during or after pregnancy, and breast cancer in men. Breast cancer risk can be altered by external factors within a few years, as shown by studies in both Norway and England during World War II, by changing rates in migrant populations, and by the effect on rates of recent adiposity. It is probable that estrogens act as promoters rather than being directly causal. Even as promoters, lifetime exposure to estrogens is not necessary. The cause is most probably a lifestyle factor, changes in which can rapidly alter risk. This has important implications in the search for a causative factor.

Group Influences on Young Adult Warfighters’ Risk-Taking

DTIC Science & Technology

2014-10-01

Characteristics, Heterosocial Relations, and Body Fat as Risk Factors for Eating Disorder Symptoms in Early Adolescence: A Causal Modeling Analysis...Reimer (1997). “The Development of Shame in Early Adolescence.” Department of Psychology, Temple University. (Winner of the 1997 Page Award for Research

The Analysis of the Contribution of Human Factors to the In-Flight Loss of Control Accidents

NASA Technical Reports Server (NTRS)

Ancel, Ersin; Shih, Ann T.

2012-01-01

In-flight loss of control (LOC) is currently the leading cause of fatal accidents based on various commercial aircraft accident statistics. As the Next Generation Air Transportation System (NextGen) emerges, new contributing factors leading to LOC are anticipated. The NASA Aviation Safety Program (AvSP), along with other aviation agencies and communities are actively developing safety products to mitigate the LOC risk. This paper discusses the approach used to construct a generic integrated LOC accident framework (LOCAF) model based on a detailed review of LOC accidents over the past two decades. The LOCAF model is comprised of causal factors from the domain of human factors, aircraft system component failures, and atmospheric environment. The multiple interdependent causal factors are expressed in an Object-Oriented Bayesian belief network. In addition to predicting the likelihood of LOC accident occurrence, the system-level integrated LOCAF model is able to evaluate the impact of new safety technology products developed in AvSP. This provides valuable information to decision makers in strategizing NASA's aviation safety technology portfolio. The focus of this paper is on the analysis of human causal factors in the model, including the contributions from flight crew and maintenance workers. The Human Factors Analysis and Classification System (HFACS) taxonomy was used to develop human related causal factors. The preliminary results from the baseline LOCAF model are also presented.

Life Strain, Social Control, Social Learning, and Delinquency: The Effects of Gender, Age, and Family SES Among Chinese Adolescents.

PubMed

Bao, Wan-Ning; Haas, Ain; Xie, Yunping

2016-09-01

Very few studies have examined the pathways to delinquency and causal factors for demographic subgroups of adolescents in a different culture. This article explores the effects of gender, age, and family socioeconomic status (SES) in an integrated model of strain, social control, social learning, and delinquency among a sample of Chinese adolescents. ANOVA is used to check for significant differences between categories of demographic groups on the variables in the integrated model, and the differential effects of causal factors in the theoretical path models are examined. Further tests of interaction effects are conducted to compare path coefficients between "high-risk" youths (i.e., male, mid-teen, and low family SES adolescents) and other subgroups. The findings identified similar pathways to delinquency across subgroups and clarified the salience of causal factors for male, mid-teen, and low SES adolescents in a different cultural context. © The Author(s) 2015.

Causal Effect of Self-esteem on Cigarette Smoking Stages in Adolescents: Coarsened Exact Matching in a Longitudinal Study.

PubMed

Khosravi, Ahmad; Mohammadpoorasl, Asghar; Holakouie-Naieni, Kourosh; Mahmoodi, Mahmood; Pouyan, Ali Akbar; Mansournia, Mohammad Ali

2016-12-01

Identification of the causal impact of self-esteem on smoking stages faces seemingly insurmountable problems in observational data, where self-esteem is not manipulable by the researcher and cannot be assigned randomly. The aim of this study was to find out if weaker self-esteem in adolescence is a risk factor of cigarette smoking in a longitudinal study in Iran. In this longitudinal study, 4,853 students (14-18 years) completed a self-administered multiple-choice anonym questionnaire. The students were evaluated twice, 12 months apart. Students were matched based on coarsened exact matching on pretreatment variables, including age, gender, smoking stages at the first wave of study, socioeconomic status, general risk-taking behavior, having a smoker in the family, having a smoker friend, attitude toward smoking, and self-injury, to ensure statistically equivalent comparison groups. Self-esteem was measured using the Rosenberg 10-item questionnaire and were classified using a latent class analysis. After matching, the effect of self-esteem was evaluated using a multinomial logistic model. In the causal fitted model, for adolescents with weaker self-esteem relative to those with stronger self-esteem, the relative risk for experimenters and regular smokers relative to nonsmokers would be expected to increase by a factor of 2.2 (1.9-2.6) and 2.0 (1.5-2.6), respectively. Using a causal approach, our study indicates that low self-esteem is consistently associated with progression in cigarette smoking stages.

Youth at Risk: A Resource for Counselors, Teachers and Parents. Part 2. Examining the Causes.

ERIC Educational Resources Information Center

Palmo, Artis J.; And Others

This document consists of Part 2 of a book of readings on at-risk youth designed to provide information and strategies for counselors, teachers, parents, administrators, social workers, and others who work with youth at risk. Part 2 contains five readings on causal factors related to at-risk behaviors. "The Harmful Effects of Dysfunctional Family…

Research on Risk Manage of Power Construction Project Based on Bayesian Network

NASA Astrophysics Data System (ADS)

Jia, Zhengyuan; Fan, Zhou; Li, Yong

With China's changing economic structure and increasingly fierce competition in the market, the uncertainty and risk factors in the projects of electric power construction are increasingly complex, the projects will face huge risks or even fail if we don't consider or ignore these risk factors. Therefore, risk management in the projects of electric power construction plays an important role. The paper emphatically elaborated the influence of cost risk in electric power projects through study overall risk management and the behavior of individual in risk management, and introduced the Bayesian network to the project risk management. The paper obtained the order of key factors according to both scene analysis and causal analysis for effective risk management.

Risk Factors of Periodontal Disease: Review of the Literature

PubMed Central

AlJehani, Yousef A.

2014-01-01

Objectives. This paper aims to review the evidence on the potential roles of modifiable and nonmodifiable risk factors associated with periodontal disease. Data. Original articles that reported on the risk factors for periodontal disease were included. Sources. MEDLINE (1980 to Jan 2014), PubMed (using medical subject headings), and Google Scholar were searched using the following terms in different combinations: “periodontal disease,” “periodontitis,” “risk factors,” and “causal.” This was supplemented by hand-searching in peer-reviewed journals and cross-referenced with the articles accessed. Conclusions. It is important to understand the etiological factors and the pathogenesis of periodontal disease to recognize and appreciate the associated risk factors. As periodontal disease is multifactorial, effective disease management requires a clear understanding of all the associated risk factors. PMID:24963294

Prenatal, Perinatal, and Neonatal Risk Factors for Specific Language Impairment: A Prospective Pregnancy Cohort Study

ERIC Educational Resources Information Center

Whitehouse, Andrew J. O.; Shelton, W. M. R.; Ing, Caleb; Newnham, John P.

2014-01-01

Purpose: Although genetic factors are known to play a causal role in specific language impairment (SLI), environmental factors may also be important. This study examined whether there are prenatal, perinatal, and neonatal factors that are associated with childhood SLI. Method: Participants were members of the Raine Study, a prospective cohort…

Stratified exact tests for the weak causal null hypothesis in randomized trials with a binary outcome.

PubMed

Chiba, Yasutaka

2017-09-01

Fisher's exact test is commonly used to compare two groups when the outcome is binary in randomized trials. In the context of causal inference, this test explores the sharp causal null hypothesis (i.e. the causal effect of treatment is the same for all subjects), but not the weak causal null hypothesis (i.e. the causal risks are the same in the two groups). Therefore, in general, rejection of the null hypothesis by Fisher's exact test does not mean that the causal risk difference is not zero. Recently, Chiba (Journal of Biometrics and Biostatistics 2015; 6: 244) developed a new exact test for the weak causal null hypothesis when the outcome is binary in randomized trials; the new test is not based on any large sample theory and does not require any assumption. In this paper, we extend the new test; we create a version of the test applicable to a stratified analysis. The stratified exact test that we propose is general in nature and can be used in several approaches toward the estimation of treatment effects after adjusting for stratification factors. The stratified Fisher's exact test of Jung (Biometrical Journal 2014; 56: 129-140) tests the sharp causal null hypothesis. This test applies a crude estimator of the treatment effect and can be regarded as a special case of our proposed exact test. Our proposed stratified exact test can be straightforwardly extended to analysis of noninferiority trials and to construct the associated confidence interval. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systemic risk and causality dynamics of the world international shipping market

NASA Astrophysics Data System (ADS)

Zhang, Xin; Podobnik, Boris; Kenett, Dror Y.; Eugene Stanley, H.

2014-12-01

Various studies have reported that many economic systems have been exhibiting an increase in the correlation between different market sectors, a factor that exacerbates the level of systemic risk. We measure this systemic risk of three major world shipping markets, (i) the new ship market, (ii) the second-hand ship market, and (iii) the freight market, as well as the shipping stock market. Based on correlation networks during three time periods, that prior to the financial crisis, during the crisis, and after the crisis, minimal spanning trees (MSTs) and hierarchical trees (HTs) both exhibit complex dynamics, i.e., different market sectors tend to be more closely linked during financial crisis. Brownian distance correlation and Granger causality test both can be used to explore the directional interconnectedness of market sectors, while Brownian distance correlation captures more dependent relationships, which are not observed in the Granger causality test. These two measures can also identify and quantify market regression periods, implying that they contain predictive power for the current crisis.

Tests of causal links between alcohol abuse or dependence and major depression.

PubMed

Fergusson, David M; Boden, Joseph M; Horwood, L John

2009-03-01

There has been a great deal of research on the comorbidity between alcohol abuse or dependence (AAD) and major depression (MD). However, it is unclear whether AAD increases the risk of MD or vice versa. To examine the associations between AAD and MD using fixed-effects modeling to control for confounding and using structural equation models to ascertain the direction of causality. Data were gathered during the course of the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of children from New Zealand (635 boys, 630 girls). General community sample. The analysis was based on a sample of 1055 participants with available data on AAD and MD at ages 17 to 18, 20 to 21, and 24 to 25 years. Symptom criteria for AAD and MD from the DSM-IV at ages 17 to 18, 20 to 21, and 24 to 25 years as well as measures of life stress, cannabis use, other illicit drug use, affiliation with deviant peers, unemployment, partner substance use, and partner criminality at ages 17 to 18, 20 to 21, and 24 to 25 years. There were significant (P < .001) pooled associations between AAD and MD. Controlling for confounding factors using conditional fixed-effects models and time-dynamic covariate factors reduced the magnitude of these associations, but they remained statistically significant. Structural equation modeling suggested that the best-fitting causal model was one in which AAD led to increased risk of MD. The findings suggest that the associations between AAD and MD were best explained by a causal model in which problems with alcohol led to increased risk of MD as opposed to a self-medication model in which MD led to increased risk of AAD.

Etiologic effects and optimal intakes of foods and nutrients for risk of cardiovascular diseases and diabetes: Systematic reviews and meta-analyses from the Nutrition and Chronic Diseases Expert Group (NutriCoDE)

PubMed Central

Peñalvo, Jose L.; Khatibzadeh, Shahab; Singh, Gitanjali M.; Rao, Mayuree; Fahimi, Saman; Powles, John; Mozaffarian, Dariush

2017-01-01

Background Dietary habits are major contributors to coronary heart disease, stroke, and diabetes. However, comprehensive evaluation of etiologic effects of dietary factors on cardiometabolic outcomes, their quantitative effects, and corresponding optimal intakes are not well-established. Objective To systematically review the evidence for effects of dietary factors on cardiometabolic diseases, including comprehensively assess evidence for causality; estimate magnitudes of etiologic effects; evaluate heterogeneity and potential for bias in these etiologic effects; and determine optimal population intake levels. Methods We utilized Bradford-Hill criteria to assess probable or convincing evidence for causal effects of multiple diet-cardiometabolic disease relationships. Etiologic effects were quantified from published or de novo meta-analyses of prospective studies or randomized clinical trials, incorporating standardized units, dose-response estimates, and heterogeneity by age and other characteristics. Potential for bias was assessed in validity analyses. Optimal intakes were determined by levels associated with lowest disease risk. Results We identified 10 foods and 7 nutrients with evidence for causal cardiometabolic effects, including protective effects of fruits, vegetables, beans/legumes, nuts/seeds, whole grains, fish, yogurt, fiber, seafood omega-3s, polyunsaturated fats, and potassium; and harms of unprocessed red meats, processed meats, sugar-sweetened beverages, glycemic load, trans-fats, and sodium. Proportional etiologic effects declined with age, but did not generally vary by sex. Established optimal population intakes were generally consistent with observed national intakes and major dietary guidelines. In validity analyses, the identified effects of individual dietary components were similar to quantified effects of dietary patterns on cardiovascular risk factors and hard endpoints. Conclusions These novel findings provide a comprehensive summary of causal evidence, quantitative etiologic effects, heterogeneity, and optimal intakes of major dietary factors for cardiometabolic diseases, informing disease impact estimation and policy planning and priorities. PMID:28448503

Aircraft Loss-of-Control Accident Analysis

NASA Technical Reports Server (NTRS)

Belcastro, Christine M.; Foster, John V.

2010-01-01

Loss of control remains one of the largest contributors to fatal aircraft accidents worldwide. Aircraft loss-of-control accidents are complex in that they can result from numerous causal and contributing factors acting alone or (more often) in combination. Hence, there is no single intervention strategy to prevent these accidents. To gain a better understanding into aircraft loss-of-control events and possible intervention strategies, this paper presents a detailed analysis of loss-of-control accident data (predominantly from Part 121), including worst case combinations of causal and contributing factors and their sequencing. Future potential risks are also considered.

The plausibility of maternal toxicant exposure and nutritional status as contributing factors to the risk of autism spectrum disorders.

PubMed

Nuttall, Johnathan R

2017-05-01

Recent research suggests the maternal environment may be especially important for the risk of developing autism spectrum disorders (ASD). In particular maternal infections, micronutrient deficiencies, obesity, and toxicant exposures are likely to interact with genetic risk factors to disrupt fetal brain development. The goal of this paper is to investigate the plausibility of maternal toxicant exposure and nutritional status as causal factors in the development of ASD. This paper reviews current research investigating the hypothesis that maternal toxicant exposure and prenatal micronutrient intake are important modifiable risk factors for ASD. Zinc, copper, iron, and vitamin B9 are identified as specific micronutrients with relevance to the etiology of ASD. Specific toxicants induce a maternal inflammatory response leading to fetal micronutrient deficiencies that disrupt early brain development. Importantly, maternal micronutrient supplementation is associated with reduced risk of ASD. Furthermore, animal studies show that micronutrient supplementation can prevent the teratogenicity and developmental neurotoxicity of specific toxicants. These findings lead to the hypothesis that maternal infection, obesity, and toxicant exposures (e.g. valproic acid, endocrine disrupting plasticizers, ethanol, and heavy metals) are all environmental risk factors for ASD that lead to fetal micronutrient deficiencies resulting from a maternal inflammatory response. It could be possible to use markers of inflammation and micronutrient status to identify women that would benefit from micronutrient supplementation or dietary interventions to reduce the risk of ASD. However, more research is needed to demonstrate a causal role of fetal micronutrient deficiencies and clarify the underlying mechanisms that contribute to ASD.

Obesity and peripheral arterial disease: A Mendelian Randomization analysis.

PubMed

Huang, Ya; Xu, Min; Xie, Lan; Wang, Tiange; Huang, Xiaolin; Lv, Xiaofei; Chen, Ying; Ding, Lin; Lin, Lin; Wang, Weiqing; Bi, Yufang; Sun, Yimin; Zhang, Yifei; Ning, Guang

2016-04-01

Observational studies showed that obesity is a major risk factor for peripheral arterial disease (PAD). However, conventional epidemiology studies are vulnerable to residual bias from confounding factors. We aimed to explore the causality of obesity in development of PAD using Mendelian Randomization (MR) approach. A MR analysis was performed in 11,477 community-dwelling adults aged 40 years and above recruited from two nearby communities during 2011-2013 in Shanghai, China. We genotyped 14 body mass index (BMI) associated common variants identified and validated in East Asians. PAD was defined as ankle-to-brachial index (ABI) <0.90 or >1.40. Weighted BMI genetic risk score (GRS) was used as the Instrumental Variable (IV). After adjusted for confounding factors, we found that each standard deviation (SD, 2.76 points) increase in BMI-GRS was associated with 0.43 (95% confidence interval [CI]: 0.36-0.49) kg/m(2) increase in BMI (P < 0.0001) and an odds ratio (OR) for PAD of 1.17 (95% CI: 1.07-1.27; P = 0.0004). Compared with the lowest quartile of BMI-GRS, the second, third and highest quartile associated with 9%, 19% and 45% increment of PAD risk, respectively (P for trend = 0.002). In the MR analysis, we demonstrated a causal relationship between obesity and PAD (OR = 1.44 per BMI-unit, 95% CI: 1.18-1.75; P = 0.0003). This study suggested that obesity may be causally associated with PAD after controlling for the potential intermediate factors like hypertension, dyslipidemia and hyperglycemia. Copyright © 2016. Published by Elsevier Ireland Ltd.

Association between Parkinson’s Disease and Cigarette Smoking, Rural Living, Well-Water Consumption, Farming and Pesticide Use: Systematic Review and Meta-Analysis

PubMed Central

Breckenridge, Charles B.; Berry, Colin; Chang, Ellen T.; Sielken, Robert L.; Mandel, Jack S.

2016-01-01

Objective Bradford Hill’s viewpoints were used to conduct a weight-of-the-evidence assessment of the association between Parkinson’s disease (PD) and rural living, farming and pesticide use. The results were compared with an assessment based upon meta-analysis. For comparison, we also evaluated the association between PD and cigarette smoking as a “positive control” because a strong inverse association has been described consistently in the literature. Methods PubMed was searched systematically to identify all published epidemiological studies that evaluated associations between Parkinson’s disease (PD) and cigarette smoking, rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides or paraquat. Studies were categorized into two study quality groups (Tier 1 or Tier 2); data were abstracted and a forest plot of relative risks (RRs) was developed for each risk factor. In addition, when available, RRs were tabulated for more highly exposed individuals compared with the unexposed. Summary RRs for each risk factor were calculated by meta-analysis of Tier 1, Tier 2 and all studies combined, with sensitivity analyses stratified by other study characteristics. Indices of between-study heterogeneity and evidence of reporting bias were assessed. Bradford Hill’s viewpoints were used to determine if a causal relationship between PD and each risk factor was supported by the weight of the evidence. Findings There was a consistent inverse (negative) association between current cigarette smoking and PD risk. In contrast, associations between PD and rural living, well-water consumption, farming and the use of pesticides, herbicides, insecticides, fungicides or paraquat were less consistent when assessed quantitatively or qualitatively. Conclusion The weight of the evidence and meta-analysis support the conclusion that there is a causal relationship between PD risk and cigarette smoking, or some unknown factor correlated with cigarette smoking. There may be risk factors associated with rural living, farming, pesticide use or well-water consumption that are causally related to PD, but the studies to date have not identified such factors. To overcome the limitations of research in this area, future studies will have to better characterize the onset of PD and its relationship to rural living, farming and exposure to pesticides. PMID:27055126

Major psychological factors affecting acceptance of gene-recombination technology.

PubMed

Tanaka, Yutaka

2004-12-01

The purpose of this study was to verify the validity of a causal model that was made to predict the acceptance of gene-recombination technology. A structural equation model was used as a causal model. First of all, based on preceding studies, the factors of perceived risk, perceived benefit, and trust were set up as important psychological factors determining acceptance of gene-recombination technology in the structural equation model. An additional factor, "sense of bioethics," which I consider to be important for acceptance of biotechnology, was added to the model. Based on previous studies, trust was set up to have an indirect influence on the acceptance of gene-recombination technology through perceived risk and perceived benefit in the model. Participants were 231 undergraduate students in Japan who answered a questionnaire with a 5-point bipolar scale. The results indicated that the proposed model fits the data well, and showed that acceptance of gene-recombination technology is explained largely by four factors, that is, perceived risk, perceived benefit, trust, and sense of bioethics, whether the technology is applied to plants, animals, or human beings. However, the relative importance of the four factors was found to vary depending on whether the gene-recombination technology was applied to plants, animals, or human beings. Specifically, the factor of sense of bioethics is the most important factor in acceptance of plant gene-recombination technology and animal gene-recombination technology, and the factors of trust and perceived risk are the most important factors in acceptance of human being gene-recombination technology.

Stress increases the risk of type 2 diabetes onset in women: A 12-year longitudinal study using causal modelling

PubMed Central

Oldmeadow, Christopher; Hure, Alexis; Luu, Judy; Loxton, Deborah

2017-01-01

Background Type 2 diabetes is associated with significant morbidity and mortality. Modifiable risk factors have been found to contribute up to 60% of type 2 diabetes risk. However, type 2 diabetes continues to rise despite implementation of interventions based on traditional risk factors. There is a clear need to identify additional risk factors for chronic disease prevention. The aim of this study was to examine the relationship between perceived stress and type 2 diabetes onset, and partition the estimates into direct and indirect effects. Methods and findings Women born in 1946–1951 (n = 12,844) completed surveys for the Australian Longitudinal Study on Women’s Health in 1998, 2001, 2004, 2007 and 2010. The total causal effect was estimated using logistic regression and marginal structural modelling. Controlled direct effects were estimated through conditioning in the regression model. A graded association was found between perceived stress and all mediators in the multivariate time lag analyses. A significant association was found between hypertension, as well as physical activity and body mass index, and diabetes, but not smoking or diet quality. Moderate/high stress levels were associated with a 2.3-fold increase in the odds of diabetes three years later, for the total estimated effect. Results were only slightly attenuated when the direct and indirect effects of perceived stress on diabetes were partitioned, with the mediators only explaining 10–20% of the excess variation in diabetes. Conclusions Perceived stress is a strong risk factor for type 2 diabetes. The majority of the effect estimate of stress on diabetes risk is not mediated by the traditional risk factors of hypertension, physical activity, smoking, diet quality, and body mass index. This gives a new pathway for diabetes prevention trials and clinical practice. PMID:28222165

A review of causal inference for biomedical informatics

PubMed Central

Kleinberg, Samantha; Hripcsak, George

2011-01-01

Causality is an important concept throughout the health sciences and is particularly vital for informatics work such as finding adverse drug events or risk factors for disease using electronic health records. While philosophers and scientists working for centuries on formalizing what makes something a cause have not reached a consensus, new methods for inference show that we can make progress in this area in many practical cases. This article reviews core concepts in understanding and identifying causality and then reviews current computational methods for inference and explanation, focusing on inference from large-scale observational data. While the problem is not fully solved, we show that graphical models and Granger causality provide useful frameworks for inference and that a more recent approach based on temporal logic addresses some of the limitations of these methods. PMID:21782035

Causal inference between bioavailability of heavy metals and environmental factors in a large-scale region.

PubMed

Liu, Yuqiong; Du, Qingyun; Wang, Qi; Yu, Huanyun; Liu, Jianfeng; Tian, Yu; Chang, Chunying; Lei, Jing

2017-07-01

The causation between bioavailability of heavy metals and environmental factors are generally obtained from field experiments at local scales at present, and lack sufficient evidence from large scales. However, inferring causation between bioavailability of heavy metals and environmental factors across large-scale regions is challenging. Because the conventional correlation-based approaches used for causation assessments across large-scale regions, at the expense of actual causation, can result in spurious insights. In this study, a general approach framework, Intervention calculus when the directed acyclic graph (DAG) is absent (IDA) combined with the backdoor criterion (BC), was introduced to identify causation between the bioavailability of heavy metals and the potential environmental factors across large-scale regions. We take the Pearl River Delta (PRD) in China as a case study. The causal structures and effects were identified based on the concentrations of heavy metals (Zn, As, Cu, Hg, Pb, Cr, Ni and Cd) in soil (0-20 cm depth) and vegetable (lettuce) and 40 environmental factors (soil properties, extractable heavy metals and weathering indices) in 94 samples across the PRD. Results show that the bioavailability of heavy metals (Cd, Zn, Cr, Ni and As) was causally influenced by soil properties and soil weathering factors, whereas no causal factor impacted the bioavailability of Cu, Hg and Pb. No latent factor was found between the bioavailability of heavy metals and environmental factors. The causation between the bioavailability of heavy metals and environmental factors at field experiments is consistent with that on a large scale. The IDA combined with the BC provides a powerful tool to identify causation between the bioavailability of heavy metals and environmental factors across large-scale regions. Causal inference in a large system with the dynamic changes has great implications for system-based risk management. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Constructionist Discourse on Resilience: Multiple Contexts, Multiple Realities among At-Risk Children and Youth

ERIC Educational Resources Information Center

Ungar, Michael

2004-01-01

An ecological approach to the study of resilience, informed by Systems Theory and emphasizing predictable relationships between risk and protective factors, circular causality, and transactional processes, is inadequate to account for the diversity of people's experiences of resilience. In contrast, a constructionist interpretation of resilience…

Risk-Based Causal Modeling of Airborne Loss of Separation

NASA Technical Reports Server (NTRS)

Geuther, Steven C.; Shih, Ann T.

2015-01-01

Maintaining safe separation between aircraft remains one of the key aviation challenges as the Next Generation Air Transportation System (NextGen) emerges. The goals of the NextGen are to increase capacity and reduce flight delays to meet the aviation demand growth through the 2025 time frame while maintaining safety and efficiency. The envisioned NextGen is expected to enable high air traffic density, diverse fleet operations in the airspace, and a decrease in separation distance. All of these factors contribute to the potential for Loss of Separation (LOS) between aircraft. LOS is a precursor to a potential mid-air collision (MAC). The NASA Airspace Operations and Safety Program (AOSP) is committed to developing aircraft separation assurance concepts and technologies to mitigate LOS instances, therefore, preventing MAC. This paper focuses on the analysis of causal and contributing factors of LOS accidents and incidents leading to MAC occurrences. Mid-air collisions among large commercial aircraft are rare in the past decade, therefore, the LOS instances in this study are for general aviation using visual flight rules in the years 2000-2010. The study includes the investigation of causal paths leading to LOS, and the development of the Airborne Loss of Separation Analysis Model (ALOSAM) using Bayesian Belief Networks (BBN) to capture the multi-dependent relations of causal factors. The ALOSAM is currently a qualitative model, although further development could lead to a quantitative model. ALOSAM could then be used to perform impact analysis of concepts and technologies in the AOSP portfolio on the reduction of LOS risk.

Estimating the Effect of Targeted Screening Strategies: An Application to Colonoscopy and Colorectal Cancer.

PubMed

Thomas, Duncan C

2017-07-01

Screening behavior depends on previous screening history and family members' behaviors, which can act as both confounders and intermediate variables on a causal pathway from screening to disease risk. Conventional analyses that adjust for these variables can lead to incorrect inferences about the causal effect of screening if high-risk individuals are more likely to be screened. Analyzing the data in a manner that treats screening as randomized conditional on covariates allows causal parameters to be estimated; inverse probability weighting based on propensity of exposure scores is one such method considered here. I simulated family data under plausible models for the underlying disease process and for screening behavior to assess the performance of alternative methods of analysis and whether a targeted screening approach based on individuals' risk factors would lead to a greater reduction in cancer incidence in the population than a uniform screening policy. Simulation results indicate that there can be a substantial underestimation of the effect of screening on subsequent cancer risk when using conventional analysis approaches, which is avoided by using inverse probability weighting. A large case-control study of colonoscopy and colorectal cancer from Germany shows a strong protective effect of screening, but inverse probability weighting makes this effect even stronger. Targeted screening approaches based on either fixed risk factors or family history yield somewhat greater reductions in cancer incidence with fewer screens needed to prevent one cancer than population-wide approaches, but the differences may not be large enough to justify the additional effort required. See video abstract at, http://links.lww.com/EDE/B207.

Sleep and Cardio-Metabolic Disease.

PubMed

Cappuccio, Francesco P; Miller, Michelle A

2017-09-19

This review summarises and discusses the epidemiological evidence suggesting a causal relationship between sleep duration and cardio-metabolic risk and outcomes in population. Sleep duration is affected by a variety of cultural, social, psychological, behavioural, pathophysiological and environmental influences. Changes in modern society-like longer working hours, more shift-work, 24/7 availability of commodities and 24-h global connectivity-have been associated with a gradual reduction in sleep duration and sleeping patterns across westernised populations. We review the evidence of an association between sleep disturbances and the development of cardio-metabolic risk and disease and discuss the implications for causality of these associations. Prolonged curtailment of sleep duration is a risk factor for the development of obesity, diabetes, hypertension, heart disease and stroke and may contribute, in the long-term, to premature death.

Non-airborne conflicts: The causes and effects of runway transgressions

NASA Technical Reports Server (NTRS)

Tarrel, Richard J.

1985-01-01

The 1210 ASRS runway transgression reports are studied and expanded to yield descriptive statistics. Additionally, a one of three subset was studied in detail for purposes of evaluating the causes, risks, and consequences behind trangression events. Occurrences are subdivided by enabling factor and flight phase designations. It is concluded that a larger risk of collision is associated with controller enabled departure transgressions over all other categories. The influence of this type is especially evident during the period following the air traffic controllers' strike of 1981. Causal analysis indicates that, coincidentally, controller enabled departure transgressions also, show the strongest correlations between causal factors. It shows that departure errors occur more often when visibility is reduced, and when multiple takeoff runways or intersection takeoffs are employed. In general, runway transgressions attributable to both pilot and controller errors arise from three problem areas: information transfer, awareness, and spatial judgement. Enhanced awareness by controllers will probably reduce controller enabled incidents.

The topology of a causal network for the Chinese financial system

NASA Astrophysics Data System (ADS)

Gao, Bo; Ren, Ruo-en

2013-07-01

The paper builds a causal network for the Chinese financial system based on the Granger causality of company risks, studies its different topologies in crisis and bull period, and applies the centrality to explain individual risk and prevent systemic risk. The results show that this causal network possesses both small-world phenomenon and scale-free property, and has a little different average distance, clustering coefficient, and degree distribution in different periods, and financial institutions with high centrality not only have large individual risk, but also are important for systemic risk immunization.

Immediately modifiable risk factors attributable to colorectal cancer in Malaysia.

PubMed

Naing, Cho; Lai, Pei Kuan; Mak, Joon Wah

2017-08-04

This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population. Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry. Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7) and the majority were men (56.6%). Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women), 10 cases (9 men, 1 woman) or 20 cases (16 men,4 women) would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369) colorectal cancer cases (42 men, 24 women) who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures. Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase physical activity, controlling body weight within normal limits and avoid alcohol intake are recommended. Future studies with other site-specific cancers and additional risk factors are needed.

Population Attributable and Preventable Fractions: Cancer Risk Factor Surveillance, and Cancer Policy Projection

PubMed Central

Shield, Kevin D.; Parkin, D. Maxwell; Whiteman, David C.; Rehm, Jürgen; Viallon, Vivian; Micallef, Claire Marant; Vineis, Paolo; Rushton, Lesley; Bray, Freddie; Soerjomataram, Isabelle

2016-01-01

The proportions of new cancer cases and deaths that are caused by exposure to risk factors and that could be prevented are key statistics for public health policy and planning. This paper summarizes the methodologies for estimating, challenges in the analysis of, and utility of, population attributable and preventable fractions for cancers caused by major risk factors such as tobacco smoking, dietary factors, high body fat, physical inactivity, alcohol consumption, infectious agents, occupational exposure, air pollution, sun exposure, and insufficient breastfeeding. For population attributable and preventable fractions, evidence of a causal relationship between a risk factor and cancer, outcome (such as incidence and mortality), exposure distribution, relative risk, theoretical-minimum-risk, and counterfactual scenarios need to be clearly defined and congruent. Despite limitations of the methodology and the data used for estimations, the population attributable and preventable fractions are a useful tool for public health policy and planning. PMID:27547696

Modelling possible causality in the associations between unemployment, cannabis use, and alcohol misuse.

PubMed

Boden, Joseph M; Lee, Jungeun Olivia; Horwood, L John; Grest, Carolina Villamil; McLeod, Geraldine F H

2017-02-01

There has been considerable interest in the extent to which substance use and unemployment may be related, particularly the causal pathways that may be involved in these associations. It has been argued that these associations may reflect social causation, in which unemployment influences substance use, or that they may reflect social selection, in which substance use increases the risk of becoming and remaining unemployed. The present study sought to test these competing explanations. Data from the Christchurch Health and Development Study, featuring a longitudinal birth cohort, were used to model the associations between unemployment and both cannabis and alcohol. Data on patterns of unemployment, involvement with cannabis, and symptoms of alcohol use disorder were examined from ages 18-35 years. The associations between unemployment and both cannabis dependence and alcohol use disorder (AUD) were modelled using conditional fixed-effects regression models, augmented by time-dynamic covariate factors. The analyses showed evidence of possible reciprocal causal processes in the association between unemployment and cannabis dependence, in which unemployment of at least three months' duration significantly (p < 0.0001) increased the risk of cannabis dependence, and cannabis dependence significantly (p < 0.0001) increased the risk of being unemployed. Similar evidence was found for the associations between unemployment and AUD, although these associations were smaller in magnitude. The present findings support both social causation and social selection arguments, by indicating that unemployment plays a causal role in substance misuse, and that it is also likely that a reverse causal process whereby substance misuse increases the risk of unemployment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigating the multi-causal and complex nature of the accident causal influence of construction project features.

PubMed

Manu, Patrick A; Ankrah, Nii A; Proverbs, David G; Suresh, Subashini

2012-09-01

Construction project features (CPFs) are organisational, physical and operational attributes that characterise construction projects. Although previous studies have examined the accident causal influence of CPFs, the multi-causal attribute of this causal phenomenon still remain elusive and thus requires further investigation. Aiming to shed light on this facet of the accident causal phenomenon of CPFs, this study examines relevant literature and crystallises the attained insight of the multi-causal attribute by a graphical model which is subsequently operationalised by a derived mathematical risk expression that offers a systematic approach for evaluating the potential of CPFs to cause harm and consequently their health and safety (H&S) risk implications. The graphical model and the risk expression put forth by the study thus advance current understanding of the accident causal phenomenon of CPFs and they present an opportunity for project participants to manage the H&S risk associated with CPFs from the early stages of project procurement. Copyright © 2011 Elsevier Ltd. All rights reserved.

Education and coronary heart disease: mendelian randomisation study.

PubMed

Tillmann, Taavi; Vaucher, Julien; Okbay, Aysu; Pikhart, Hynek; Peasey, Anne; Kubinova, Ruzena; Pajak, Andrzej; Tamosiunas, Abdonas; Malyutina, Sofia; Hartwig, Fernando Pires; Fischer, Krista; Veronesi, Giovanni; Palmer, Tom; Bowden, Jack; Davey Smith, George; Bobak, Martin; Holmes, Michael V

2017-08-30

Objective  To determine whether educational attainment is a causal risk factor in the development of coronary heart disease. Design  Mendelian randomisation study, using genetic data as proxies for education to minimise confounding. Setting  The main analysis used genetic data from two large consortia (CARDIoGRAMplusC4D and SSGAC), comprising 112 studies from predominantly high income countries. Findings from mendelian randomisation analyses were then compared against results from traditional observational studies (164 170 participants). Finally, genetic data from six additional consortia were analysed to investigate whether longer education can causally alter the common cardiovascular risk factors. Participants  The main analysis was of 543 733 men and women (from CARDIoGRAMplusC4D and SSGAC), predominantly of European origin. Exposure  A one standard deviation increase in the genetic predisposition towards higher education (3.6 years of additional schooling), measured by 162 genetic variants that have been previously associated with education. Main outcome measure  Combined fatal and non-fatal coronary heart disease (63 746 events in CARDIoGRAMplusC4D). Results  Genetic predisposition towards 3.6 years of additional education was associated with a one third lower risk of coronary heart disease (odds ratio 0.67, 95% confidence interval 0.59 to 0.77; P=3×10 -8 ). This was comparable to findings from traditional observational studies (prevalence odds ratio 0.73, 0.68 to 0.78; incidence odds ratio 0.80, 0.76 to 0.83). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely, although this remains an untestable possibility. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index, and a favourable blood lipid profile. Conclusions  This mendelian randomisation study found support for the hypothesis that low education is a causal risk factor in the development of coronary heart disease. Potential mechanisms could include smoking, body mass index, and blood lipids. In conjunction with the results from studies with other designs, these findings suggest that increasing education may result in substantial health benefits.

Education and coronary heart disease: mendelian randomisation study

PubMed Central

Vaucher, Julien; Okbay, Aysu; Pikhart, Hynek; Peasey, Anne; Kubinova, Ruzena; Pajak, Andrzej; Tamosiunas, Abdonas; Malyutina, Sofia; Hartwig, Fernando Pires; Fischer, Krista; Veronesi, Giovanni; Palmer, Tom; Bowden, Jack; Davey Smith, George; Bobak, Martin; Holmes, Michael V

2017-01-01

Objective To determine whether educational attainment is a causal risk factor in the development of coronary heart disease. Design Mendelian randomisation study, using genetic data as proxies for education to minimise confounding. Setting The main analysis used genetic data from two large consortia (CARDIoGRAMplusC4D and SSGAC), comprising 112 studies from predominantly high income countries. Findings from mendelian randomisation analyses were then compared against results from traditional observational studies (164 170 participants). Finally, genetic data from six additional consortia were analysed to investigate whether longer education can causally alter the common cardiovascular risk factors. Participants The main analysis was of 543 733 men and women (from CARDIoGRAMplusC4D and SSGAC), predominantly of European origin. Exposure A one standard deviation increase in the genetic predisposition towards higher education (3.6 years of additional schooling), measured by 162 genetic variants that have been previously associated with education. Main outcome measure Combined fatal and non-fatal coronary heart disease (63 746 events in CARDIoGRAMplusC4D). Results Genetic predisposition towards 3.6 years of additional education was associated with a one third lower risk of coronary heart disease (odds ratio 0.67, 95% confidence interval 0.59 to 0.77; P=3×10−8). This was comparable to findings from traditional observational studies (prevalence odds ratio 0.73, 0.68 to 0.78; incidence odds ratio 0.80, 0.76 to 0.83). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely, although this remains an untestable possibility. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index, and a favourable blood lipid profile. Conclusions This mendelian randomisation study found support for the hypothesis that low education is a causal risk factor in the development of coronary heart disease. Potential mechanisms could include smoking, body mass index, and blood lipids. In conjunction with the results from studies with other designs, these findings suggest that increasing education may result in substantial health benefits. PMID:28855160

Evidence for the Convergence Model: The Emergence of Highly Pathogenic Avian Influenza (H5N1) in Viet Nam

PubMed Central

Saksena, Sumeet; Fox, Jefferson; Epprecht, Michael; Tran, Chinh C.; Nong, Duong H.; Spencer, James H.; Nguyen, Lam; Finucane, Melissa L.; Tran, Vien D.; Wilcox, Bruce A.

2015-01-01

Building on a series of ground breaking reviews that first defined and drew attention to emerging infectious diseases (EID), the ‘convergence model’ was proposed to explain the multifactorial causality of disease emergence. The model broadly hypothesizes disease emergence is driven by the co-incidence of genetic, physical environmental, ecological, and social factors. We developed and tested a model of the emergence of highly pathogenic avian influenza (HPAI) H5N1 based on suspected convergence factors that are mainly associated with land-use change. Building on previous geospatial statistical studies that identified natural and human risk factors associated with urbanization, we added new factors to test whether causal mechanisms and pathogenic landscapes could be more specifically identified. Our findings suggest that urbanization spatially combines risk factors to produce particular types of peri-urban landscapes with significantly higher HPAI H5N1 emergence risk. The work highlights that peri-urban areas of Viet Nam have higher levels of chicken densities, duck and geese flock size diversities, and fraction of land under rice or aquaculture than rural and urban areas. We also found that land-use diversity, a surrogate measure for potential mixing of host populations and other factors that likely influence viral transmission, significantly improves the model’s predictability. Similarly, landscapes where intensive and extensive forms of poultry production overlap were found at greater risk. These results support the convergence hypothesis in general and demonstrate the potential to improve EID prevention and control by combing geospatial monitoring of these factors along with pathogen surveillance programs. PMID:26398118

Common variants associated with plasma triglycerides and risk for coronary artery disease.

PubMed

Do, Ron; Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Müller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Döring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J F; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Altshuler, David; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L; Ingelsson, Erik; Abecasis, Goncalo R; Daly, Mark J; Neale, Benjamin M; Kathiresan, Sekar

2013-11-01

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

Common variants associated with plasma triglycerides and risk for coronary artery disease

PubMed Central

Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tõnu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Müller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Döring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J.F.; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; März, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njølstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.; Ripatti, Samuli; Cupples, L. Adrienne; Sandhu, Manjinder S.; Rich, Stephen S.; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L.; Ingelsson, Erik; Abecasis, Goncalo R.; Daly, Mark J.; Neale, Benjamin M.; Kathiresan, Sekar

2013-01-01

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5×10−8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064

Bone mineral density and risk of type 2 diabetes and coronary heart disease: A Mendelian randomization study.

PubMed

Gan, Wei; Clarke, Robert J; Mahajan, Anubha; Kulohoma, Benard; Kitajima, Hidetoshi; Robertson, Neil R; Rayner, N William; Walters, Robin G; Holmes, Michael V; Chen, Zhengming; McCarthy, Mark I

2017-01-01

Background: Observational studies have demonstrated that increased bone mineral density is associated with a higher risk of type 2 diabetes (T2D), but the relationship with risk of coronary heart disease (CHD) is less clear. Moreover, substantial uncertainty remains about the causal relevance of increased bone mineral density for T2D and CHD, which can be assessed by Mendelian randomisation studies.  Methods: We identified 235 independent single nucleotide polymorphisms (SNPs) associated at p <5×10 -8 with estimated heel bone mineral density (eBMD) in 116,501 individuals from the UK Biobank study, accounting for 13.9% of eBMD variance. For each eBMD-associated SNP, we extracted effect estimates from the largest available GWAS studies for T2D (DIAGRAM: n=26,676 T2D cases and 132,532 controls) and CHD (CARDIoGRAMplusC4D: n=60,801 CHD cases and 123,504 controls). A two-sample design using several Mendelian randomization approaches was used to investigate the causal relevance of eBMD for risk of T2D and CHD. In addition, we explored the relationship of eBMD, instrumented by the 235 SNPs, on 12 cardiovascular and metabolic risk factors. Finally, we conducted Mendelian randomization analysis in the reverse direction to investigate reverse causality. Results: Each one standard deviation increase in genetically instrumented eBMD (equivalent to 0.14 g/cm 2 ) was associated with an 8% higher risk of T2D (odds ratio [OR] 1.08; 95% confidence interval [CI]: 1.02 to 1.14; p =0.012) and 5% higher risk of CHD (OR 1.05; 95%CI: 1.00 to 1.10; p =0.034). Consistent results were obtained in sensitivity analyses using several different Mendelian randomization approaches. Equivalent increases in eBMD were also associated with lower plasma levels of HDL-cholesterol and increased insulin resistance. Mendelian randomization in the reverse direction using 94 T2D SNPs or 52 CHD SNPs showed no evidence of reverse causality with eBMD. Conclusions: These findings suggest a causal relationship between elevated bone mineral density with risks of both T2D and CHD.

Use of allele scores as instrumental variables for Mendelian randomization

PubMed Central

Burgess, Stephen; Thompson, Simon G

2013-01-01

Background An allele score is a single variable summarizing multiple genetic variants associated with a risk factor. It is calculated as the total number of risk factor-increasing alleles for an individual (unweighted score), or the sum of weights for each allele corresponding to estimated genetic effect sizes (weighted score). An allele score can be used in a Mendelian randomization analysis to estimate the causal effect of the risk factor on an outcome. Methods Data were simulated to investigate the use of allele scores in Mendelian randomization where conventional instrumental variable techniques using multiple genetic variants demonstrate ‘weak instrument’ bias. The robustness of estimates using the allele score to misspecification (for example non-linearity, effect modification) and to violations of the instrumental variable assumptions was assessed. Results Causal estimates using a correctly specified allele score were unbiased with appropriate coverage levels. The estimates were generally robust to misspecification of the allele score, but not to instrumental variable violations, even if the majority of variants in the allele score were valid instruments. Using a weighted rather than an unweighted allele score increased power, but the increase was small when genetic variants had similar effect sizes. Naive use of the data under analysis to choose which variants to include in an allele score, or for deriving weights, resulted in substantial biases. Conclusions Allele scores enable valid causal estimates with large numbers of genetic variants. The stringency of criteria for genetic variants in Mendelian randomization should be maintained for all variants in an allele score. PMID:24062299

A review of covariate selection for non-experimental comparative effectiveness research.

PubMed

Sauer, Brian C; Brookhart, M Alan; Roy, Jason; VanderWeele, Tyler

2013-11-01

This paper addresses strategies for selecting variables for adjustment in non-experimental comparative effectiveness research and uses causal graphs to illustrate the causal network that relates treatment to outcome. Variables in the causal network take on multiple structural forms. Adjustment for a common cause pathway between treatment and outcome can remove confounding, whereas adjustment for other structural types may increase bias. For this reason, variable selection would ideally be based on an understanding of the causal network; however, the true causal network is rarely known. Therefore, we describe more practical variable selection approaches based on background knowledge when the causal structure is only partially known. These approaches include adjustment for all observed pretreatment variables thought to have some connection to the outcome, all known risk factors for the outcome, and all direct causes of the treatment or the outcome. Empirical approaches, such as forward and backward selection and automatic high-dimensional proxy adjustment, are also discussed. As there is a continuum between knowing and not knowing the causal, structural relations of variables, we recommend addressing variable selection in a practical way that involves a combination of background knowledge and empirical selection and that uses high-dimensional approaches. This empirical approach can be used to select from a set of a priori variables based on the researcher's knowledge to be included in the final analysis or to identify additional variables for consideration. This more limited use of empirically derived variables may reduce confounding while simultaneously reducing the risk of including variables that may increase bias. Copyright © 2013 John Wiley & Sons, Ltd.

A Review of Covariate Selection for Nonexperimental Comparative Effectiveness Research

PubMed Central

Sauer, Brian C.; Brookhart, Alan; Roy, Jason; Vanderweele, Tyler

2014-01-01

This paper addresses strategies for selecting variables for adjustment in non-experimental comparative effectiveness research (CER), and uses causal graphs to illustrate the causal network that relates treatment to outcome. Variables in the causal network take on multiple structural forms. Adjustment for on a common cause pathway between treatment and outcome can remove confounding, while adjustment for other structural types may increase bias. For this reason variable selection would ideally be based on an understanding of the causal network; however, the true causal network is rarely know. Therefore, we describe more practical variable selection approaches based on background knowledge when the causal structure is only partially known. These approaches include adjustment for all observed pretreatment variables thought to have some connection to the outcome, all known risk factors for the outcome, and all direct causes of the treatment or the outcome. Empirical approaches, such as forward and backward selection and automatic high-dimensional proxy adjustment, are also discussed. As there is a continuum between knowing and not knowing the causal, structural relations of variables, we recommend addressing variable selection in a practical way that involves a combination of background knowledge and empirical selection and that uses the high-dimensional approaches. This empirical approach can be used to select from a set of a priori variables based on the researcher’s knowledge to be included in the final analysis or to identify additional variables for consideration. This more limited use of empirically-derived variables may reduce confounding while simultaneously reducing the risk of including variables that may increase bias. PMID:24006330

Incest in Context.

ERIC Educational Resources Information Center

Taubman, Stan

1984-01-01

Presents a comprehensive view of the societal, cultural, familial, and personality factors that form the context of people at risk for incest and associated problems. Summarizes the consequences and the causal context of incest and describes an ecosystems approach to intervention. (Author/LLL)

A Children of Twins Study of parental divorce and offspring psychopathology.

PubMed

D'Onofrio, Brian M; Turkheimer, Eric; Emery, Robert E; Maes, Hermine H; Silberg, Judy; Eaves, Lindon J

2007-07-01

Although parental divorce is associated with increased substance use and internalizing problems, experiencing the separation of one's parents may not cause these outcomes. The relations may be due to genetic or environmental selection factors, characteristics that lead to both marital separation and offspring functioning. We used the Children of Twins (CoT) Design to explore whether unmeasured genetic or environmental factors related to the twin parent, and measured characteristics of both parents, account for the association between parental divorce and offspring substance use and internalizing problems. The association between parental divorce and offspring substance use problems remained robust when controlling for genetic and environmental risk from the twin parent associated with parental divorce, and measured characteristics of both parents. The results do not prove, but are consistent with, a causal connection. In contrast, the analyses suggest that shared genetic liability in parents and their offspring accounts for the increased risk of internalizing problems in adult offspring from divorced families. The study illustrates that unmeasured genetic and environmental selection factors must be considered when studying parental divorce. In explaining associations between parental divorce and young-adult adjustment, our evidence suggests that selection versus causal mechanisms may operate differently for substance abuse (a causal relation) and internalizing problems (an artifact of selection). The CoT design only controls for the genetic and environmental characteristics of one parent; thus, additional genetically informed analyses are needed.

A new pressure ulcer conceptual framework.

PubMed

Coleman, Susanne; Nixon, Jane; Keen, Justin; Wilson, Lyn; McGinnis, Elizabeth; Dealey, Carol; Stubbs, Nikki; Farrin, Amanda; Dowding, Dawn; Schols, Jos M G A; Cuddigan, Janet; Berlowitz, Dan; Jude, Edward; Vowden, Peter; Schoonhoven, Lisette; Bader, Dan L; Gefen, Amit; Oomens, Cees W J; Nelson, E Andrea

2014-10-01

This paper discusses the critical determinants of pressure ulcer development and proposes a new pressure ulcer conceptual framework. Recent work to develop and validate a new evidence-based pressure ulcer risk assessment framework was undertaken. This formed part of a Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056), funded by the National Institute for Health Research. The foundation for the risk assessment component incorporated a systematic review and a consensus study that highlighted the need to propose a new conceptual framework. Discussion Paper. The new conceptual framework links evidence from biomechanical, physiological and epidemiological evidence, through use of data from a systematic review (search conducted March 2010), a consensus study (conducted December 2010-2011) and an international expert group meeting (conducted December 2011). A new pressure ulcer conceptual framework incorporating key physiological and biomechanical components and their impact on internal strains, stresses and damage thresholds is proposed. Direct and key indirect causal factors suggested in a theoretical causal pathway are mapped to the physiological and biomechanical components of the framework. The new proposed conceptual framework provides the basis for understanding the critical determinants of pressure ulcer development and has the potential to influence risk assessment guidance and practice. It could also be used to underpin future research to explore the role of individual risk factors conceptually and operationally. By integrating existing knowledge from epidemiological, physiological and biomechanical evidence, a theoretical causal pathway and new conceptual framework are proposed with potential implications for practice and research. © 2014 The Authors. Journal of Advanced Nursing Published by John Wiley & Sons Ltd.

A new pressure ulcer conceptual framework

PubMed Central

Coleman, Susanne; Nixon, Jane; Keen, Justin; Wilson, Lyn; McGinnis, Elizabeth; Dealey, Carol; Stubbs, Nikki; Farrin, Amanda; Dowding, Dawn; Schols, Jos MGA; Cuddigan, Janet; Berlowitz, Dan; Jude, Edward; Vowden, Peter; Schoonhoven, Lisette; Bader, Dan L; Gefen, Amit; Oomens, Cees WJ; Nelson, E Andrea

2014-01-01

Aim This paper discusses the critical determinants of pressure ulcer development and proposes a new pressure ulcer conceptual framework. Background Recent work to develop and validate a new evidence-based pressure ulcer risk assessment framework was undertaken. This formed part of a Pressure UlceR Programme Of reSEarch (RP-PG-0407-10056), funded by the National Institute for Health Research. The foundation for the risk assessment component incorporated a systematic review and a consensus study that highlighted the need to propose a new conceptual framework. Design Discussion Paper. Data Sources The new conceptual framework links evidence from biomechanical, physiological and epidemiological evidence, through use of data from a systematic review (search conducted March 2010), a consensus study (conducted December 2010–2011) and an international expert group meeting (conducted December 2011). Implications for Nursing A new pressure ulcer conceptual framework incorporating key physiological and biomechanical components and their impact on internal strains, stresses and damage thresholds is proposed. Direct and key indirect causal factors suggested in a theoretical causal pathway are mapped to the physiological and biomechanical components of the framework. The new proposed conceptual framework provides the basis for understanding the critical determinants of pressure ulcer development and has the potential to influence risk assessment guidance and practice. It could also be used to underpin future research to explore the role of individual risk factors conceptually and operationally. Conclusion By integrating existing knowledge from epidemiological, physiological and biomechanical evidence, a theoretical causal pathway and new conceptual framework are proposed with potential implications for practice and research. PMID:24684197

Body Investment, Depression, and Alcohol Use as Risk Factors for Suicide Proneness in College Students

PubMed Central

Lamis, Dorian A.; Malone, Patrick S.; Langhinrichsen-Rohling, Jennifer; Ellis, Thomas E.

2009-01-01

This study examined the relationships among three risk factors – body investment, depression, and alcohol use – and suicide proneness as measured by the Life Attitudes Schedule – Short Form (LAS-SF) in college students (n = 318). Path analysis was used to construct a causal model of suicide proneness. The Body Investment Scale (BIS) subscales were assumed to be causally prior to depression, which was in turn modeled as occurring prior to alcohol use, which was in turn modeled as prior to suicide proneness. Results revealed that, as expected suicide proneness was positively predicted by alcohol use, alcohol use was positively predicted by depression, and depression was negatively predicted by the body image component of the BIS. Additionally, the body image-suicide proneness link was significantly mediated by depression and its direct effect on suicide proneness as well as by the two-mediator path of body image on depression on drinking on suicide proneness. Implications are offered for the improved identification and treatment of young adults at risk for suicidal and health-diminishing behaviors. PMID:20573605

Modeling for the allocation of oil spill recovery capacity considering environmental and economic factors.

PubMed

Ha, Min-Jae

2018-01-01

This study presents a regional oil spill risk assessment and capacities for marine oil spill response in Korea. The risk assessment of oil spill is carried out using both causal factors and environmental/economic factors. The weight of each parameter is calculated using the Analytic Hierarchy Process (AHP). Final regional risk degrees of oil spill are estimated by combining the degree and weight of each existing parameter. From these estimated risk levels, oil recovery capacities were determined with reference to the recovery target of 7500kl specified in existing standards. The estimates were deemed feasible, and provided a more balanced distribution of resources than existing capacities set according to current standards. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identifying Causal Variants at Loci with Multiple Signals of Association

PubMed Central

Hormozdiari, Farhad; Kostem, Emrah; Kang, Eun Yong; Pasaniuc, Bogdan; Eskin, Eleazar

2014-01-01

Although genome-wide association studies have successfully identified thousands of risk loci for complex traits, only a handful of the biologically causal variants, responsible for association at these loci, have been successfully identified. Current statistical methods for identifying causal variants at risk loci either use the strength of the association signal in an iterative conditioning framework or estimate probabilities for variants to be causal. A main drawback of existing methods is that they rely on the simplifying assumption of a single causal variant at each risk locus, which is typically invalid at many risk loci. In this work, we propose a new statistical framework that allows for the possibility of an arbitrary number of causal variants when estimating the posterior probability of a variant being causal. A direct benefit of our approach is that we predict a set of variants for each locus that under reasonable assumptions will contain all of the true causal variants with a high confidence level (e.g., 95%) even when the locus contains multiple causal variants. We use simulations to show that our approach provides 20–50% improvement in our ability to identify the causal variants compared to the existing methods at loci harboring multiple causal variants. We validate our approach using empirical data from an expression QTL study of CHI3L2 to identify new causal variants that affect gene expression at this locus. CAVIAR is publicly available online at http://genetics.cs.ucla.edu/caviar/. PMID:25104515

Identifying causal variants at loci with multiple signals of association.

PubMed

Hormozdiari, Farhad; Kostem, Emrah; Kang, Eun Yong; Pasaniuc, Bogdan; Eskin, Eleazar

2014-10-01

Although genome-wide association studies have successfully identified thousands of risk loci for complex traits, only a handful of the biologically causal variants, responsible for association at these loci, have been successfully identified. Current statistical methods for identifying causal variants at risk loci either use the strength of the association signal in an iterative conditioning framework or estimate probabilities for variants to be causal. A main drawback of existing methods is that they rely on the simplifying assumption of a single causal variant at each risk locus, which is typically invalid at many risk loci. In this work, we propose a new statistical framework that allows for the possibility of an arbitrary number of causal variants when estimating the posterior probability of a variant being causal. A direct benefit of our approach is that we predict a set of variants for each locus that under reasonable assumptions will contain all of the true causal variants with a high confidence level (e.g., 95%) even when the locus contains multiple causal variants. We use simulations to show that our approach provides 20-50% improvement in our ability to identify the causal variants compared to the existing methods at loci harboring multiple causal variants. We validate our approach using empirical data from an expression QTL study of CHI3L2 to identify new causal variants that affect gene expression at this locus. CAVIAR is publicly available online at http://genetics.cs.ucla.edu/caviar/. Copyright © 2014 by the Genetics Society of America.

The HABP2 G534E polymorphism does not increase nonmedullary thyroid cancer risk in Hispanics

PubMed Central

Bohórquez, Mabel E; Estrada, Ana P; Stultz, Jacob; Sahasrabudhe, Ruta; Williamson, John; Lott, Paul; Duque, Carlos S; Donado, Jorge; Mateus, Gilbert; Bolaños, Fernando; Vélez, Alejandro; Echeverry, Magdalena

2016-01-01

Familial nonmedullary thyroid cancer (NMTC) has not been clearly linked to causal germline variants, despite the large role that genetic factors play in risk. Recently, HABP2 G534E (rs7080536A) has been implicated as a causal variant in NMTC. We have previously shown that the HABP2 G534E variant is not associated with TC risk in patients from the British Isles. Hispanics are the largest and the youngest minority in the United States and NMTC is now the second most common malignancy in women from this population. In order to determine if the HABP2 G534E variant played a role in NMTC risk among Hispanic populations, we analyzed 281 cases and 1105 population-matched controls from a multicenter study in Colombia, evaluating the association through logistic regression. We found that the HABP2 G534E variant was not significantly associated with NMTC risk (P=0.843) in this Hispanic group. We also stratified available clinical data by multiple available clinicopathological variables and further analyzed the effect of HABP2 on NMTC presentation. However, we failed to detect associations between HABP2 G534E and NMTC risk, regardless of disease presentation (P≥0.273 for all cases). Therefore, without any significant associations between the HABP2 G534E variant and NMTC risk, we conclude that the variant is not causal of NMTC in this Hispanic population. PMID:27097599

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study.

PubMed

Østergaard, Søren D; Mukherjee, Shubhabrata; Sharp, Stephen J; Proitsi, Petroula; Lotta, Luca A; Day, Felix; Perry, John R B; Boehme, Kevin L; Walter, Stefan; Kauwe, John S; Gibbons, Laura E; Larson, Eric B; Powell, John F; Langenberg, Claudia; Crane, Paul K; Wareham, Nicholas J; Scott, Robert A

2015-06-01

Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, NSNPs = 49), fasting glucose (NSNPs = 36), insulin resistance (NSNPs = 10), body mass index (BMI, NSNPs = 32), total cholesterol (NSNPs = 73), HDL-cholesterol (NSNPs = 71), LDL-cholesterol (NSNPs = 57), triglycerides (NSNPs = 39), systolic blood pressure (SBP, NSNPs = 24), smoking initiation (NSNPs = 1), smoking quantity (NSNPs = 3), university completion (NSNPs = 2), and years of education (NSNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP-AD associations from the International Genomics of Alzheimer's Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62-0.91]; p = 3.4 × 10(-3)). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10(-8)). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51-0.89]; p = 6.5 × 10(-3)), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses. Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure--or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications--may reduce AD risk.

Anxiety Disorders and Sensory Over-Responsivity in Children with Autism Spectrum Disorders: Is There a Causal Relationship?

PubMed Central

Ben-Sasson, Ayelet

2010-01-01

Anxiety disorders and sensory over-responsivity (SOR) are common in children with autism spectrum disorders (ASD), and there is evidence for an association between these two conditions. Currently, it is unclear what causal mechanisms may exist between SOR and anxiety. We propose three possible theories to explain the association between anxiety and SOR: (a) SOR is caused by anxiety; (b) Anxiety is caused by SOR; or (c) SOR and anxiety are causally unrelated but are associated through a common risk factor or diagnostic overlap. In this paper, we examine support for each theory in the existing anxiety, autism, and neuroscience literature, and discuss how each theory informs choice of interventions and implications for future studies. PMID:20383658

Estimating causal contrasts involving intermediate variables in the presence of selection bias.

PubMed

Valeri, Linda; Coull, Brent A

2016-11-20

An important goal across the biomedical and social sciences is the quantification of the role of intermediate factors in explaining how an exposure exerts an effect on an outcome. Selection bias has the potential to severely undermine the validity of inferences on direct and indirect causal effects in observational as well as in randomized studies. The phenomenon of selection may arise through several mechanisms, and we here focus on instances of missing data. We study the sign and magnitude of selection bias in the estimates of direct and indirect effects when data on any of the factors involved in the analysis is either missing at random or not missing at random. Under some simplifying assumptions, the bias formulae can lead to nonparametric sensitivity analyses. These sensitivity analyses can be applied to causal effects on the risk difference and risk-ratio scales irrespectively of the estimation approach employed. To incorporate parametric assumptions, we also develop a sensitivity analysis for selection bias in mediation analysis in the spirit of the expectation-maximization algorithm. The approaches are applied to data from a health disparities study investigating the role of stage at diagnosis on racial disparities in colorectal cancer survival. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Some (But Not Much) Progress Toward Understanding Teenage Childbearing: A Review of Research From the Past Decade

PubMed Central

Coyne, Claire A.; D’Onofrio, Brian M.

2013-01-01

In the decade and a half since Coley & Chase-Lansdale’s (1998) review of teenage childbearing there have been a number of studies investigating teenage childbearing from a developmental psychological perspective. Many of these studies have focused primarily on identifying individual, familial, and socioeconomic risk factors in childhood and adolescence that are highly correlated with teenage sexual behavior and teenage childbearing. We have an emerging understanding of teenage childbearing as the culmination of a complex cascade of experiences and decisions that overlap greatly with the risks for antisocial behavior. Much of this research, however, is limited by its reliance on correlational and cross-sectional research designs, which are not able to rigorously test causal inferences or to identify mechanisms associated with teenage childbearing. Innovative studies using large, nationally representative samples with quasi-experimental and longitudinal designs can expand on such descriptive studies. In particular, quasi-experimental studies can help answer questions about which risk factors are causally associated with teenage childbearing and suggest potential mechanisms that can explain how teenage childbearing is associated with poor outcomes. Future studies also will need to incorporate more precise measures of developmental processes and explore heterogeneity among adolescent mothers. Although advances have been made in the psychological study of teenage childbearing, more research is needed in order to answer important questions about which psychological processes are causally related to teenage childbearing and how teenage childbearing is associated with poor outcomes for young mothers and their offspring. PMID:22675905

Risk and protective factors for the development of childhood asthma.

PubMed

Ding, Guodong; Ji, Ruoxu; Bao, Yixiao

2015-03-01

Childhood asthma prevalence worldwide has been increasing markedly over several decades. Various theories have been proposed to account for this alarming trend. The disease has a broad spectrum of potential determinants ranging from genetics to lifestyle and environmental factors. Epidemiological observations have demonstrated that several important lifestyle and environmental factors including obesity, urban living, dietary patterns such as food low in antioxidants and fast food, non-breastfeeding, gut flora imbalance, cigarette smoking, air pollution, and viral infection are associated with asthma exacerbations in children. However, only environmental tobacco smoke has been associated with the development of asthma. Despite epidemiological studies indicating that many other factors are probably associated with the development of asthma, the relationships are not considered causal due to the inadequate evidence and inconsistent results from recent studies. This may highlight that sufficient data and exact mechanisms of causality are still in need of further study. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of risk factors for and components of metabolic syndrome on the quality of life of patients with systemic lupus erythematosus: a structural equation modeling approach.

PubMed

Lee, Jeong-Won; Kang, Ji-Hyoun; Lee, Kyung-Eun; Park, Dong-Jin; Kang, Seong Wook; Kwok, Seung-Ki; Kim, Seong-Kyu; Choe, Jung-Yoon; Kim, Hyoun-Ah; Sung, Yoon-Kyoung; Shin, Kichul; Lee, Sang-Il; Lee, Chang Hoon; Choi, Sung Jae; Lee, Shin-Seok

2018-01-01

This study assessed the relationships among the risk factors for and components of metabolic syndrome (MetS) and health-related quality of life (HRQOL) in a hypothesized causal model using structural equation modeling (SEM) in patients with systemic lupus erythematosus (SLE). Of the 505 SLE patients enrolled in the Korean Lupus Network (KORNET registry), 244 had sufficient data to assess the components of MetS at enrollment. Education level, monthly income, corticosteroid dose, Systemic Lupus Erythematosus Disease Activity Index, Physicians' Global Assessment, Beck Depression Inventory, MetS components, and the Short Form-36 at the time of cohort entry were determined. SEM was used to test the causal relationship based on the Analysis of Moment Structure. The average age of the 244 patients was 40.7 ± 11.8 years. The SEM results supported the good fit of the model (χ 2  = 71.629, p = 0.078, RMSEA 0.034, CFI 0.972). The final model showed a direct negative effect of higher socioeconomic status and a positive indirect effect of higher disease activity on MetS, the latter through corticosteroid dose. MetS did not directly impact HRQOL but had an indirect negative impact on it, through depression. In our causal model, MetS risk factors were related to MetS components. The latter had a negative indirect impact on HRQOL, through depression. Clinicians should consider socioeconomic status and medication and seek to modify disease activity, MetS, and depression to improve the HRQOL of SLE patients.

Spatiotemporal causal modeling for the management of Dengue Fever

NASA Astrophysics Data System (ADS)

Yu, Hwa-Lung; Huang, Tailin; Lee, Chieh-Han

2015-04-01

Increasing climatic extremes have caused growing concerns about the health effects and disease outbreaks. The association between climate variation and the occurrence of epidemic diseases play an important role on a country's public health systems. Part of the impacts are direct casualties associated with the increasing frequency and intensity of typhoons, the proliferation of disease vectors and the short-term increase of clinic visits on gastro-intestinal discomforts, diarrhea, dermatosis, or psychological trauma. Other impacts come indirectly from the influence of disasters on the ecological and socio-economic systems, including the changes of air/water quality, living environment and employment condition. Previous risk assessment studies on dengue fever focus mostly on climatic and non-climatic factors and their association with vectors' reproducing pattern. The public-health implication may appear simple. Considering the seasonal changes and regional differences, however, the causality of the impacts is full of uncertainties. Without further investigation, the underlying dengue fever risk dynamics may not be assessed accurately. The objective of this study is to develop an epistemic framework for assessing dynamic dengue fever risk across space and time. The proposed framework integrates cross-departmental data, including public-health databases, precipitation data over time and various socio-economic data. We explore public-health issues induced by typhoon through literature review and spatiotemporal analytic techniques on public health databases. From those data, we identify relevant variables and possible causal relationships, and their spatiotemporal patterns derived from our proposed spatiotemporal techniques. Eventually, we create a spatiotemporal causal network and a framework for modeling dynamic dengue fever risk.

A general, multivariate definition of causal effects in epidemiology.

PubMed

Flanders, W Dana; Klein, Mitchel

2015-07-01

Population causal effects are often defined as contrasts of average individual-level counterfactual outcomes, comparing different exposure levels. Common examples include causal risk difference and risk ratios. These and most other examples emphasize effects on disease onset, a reflection of the usual epidemiological interest in disease occurrence. Exposure effects on other health characteristics, such as prevalence or conditional risk of a particular disability, can be important as well, but contrasts involving these other measures may often be dismissed as non-causal. For example, an observed prevalence ratio might often viewed as an estimator of a causal incidence ratio and hence subject to bias. In this manuscript, we provide and evaluate a definition of causal effects that generalizes those previously available. A key part of the generalization is that contrasts used in the definition can involve multivariate, counterfactual outcomes, rather than only univariate outcomes. An important consequence of our generalization is that, using it, one can properly define causal effects based on a wide variety of additional measures. Examples include causal prevalence ratios and differences and causal conditional risk ratios and differences. We illustrate how these additional measures can be useful, natural, easily estimated, and of public health importance. Furthermore, we discuss conditions for valid estimation of each type of causal effect, and how improper interpretation or inferences for the wrong target population can be sources of bias.

Has patient survival following renal transplantation improved in the era of modern immunosuppression?

PubMed

Hernández, Domingo; Moreso, Francesc

2013-01-01

Renal transplantation (TX) is the treatment of choice in the majority of patients with chronic kidney disease. But, these patients have a high mortality rate with respect to the general population despite new immunosuppression treatments and improved clinical management. This justifies that the excellent results obtained in the short terms do not have a parallel clinical benefit in the long term. This worrying situation is probably due to a high prevalence of cardiovascular conditions and infectious and neoplastic entities amongst this population against a backdrop of immunosuppression treatment. Furthermore, there is interaction between these processes, which share causal factors and common pathogenic mechanisms. Mortality thus increases. Therefore, identifying the causes of death and the risk factors, applying morbidity and mortality predictive models and intervening in causal factors could constitute some of the strategies for improving renal transplantation results in terms of survival. This review analyses some of the evidence conditioning this high mortality rate following TX, as well and the therapeutic and prognostic aspects associated with co-morbidity: 1) Magnitude of the problem and causes of death among sufferers; 2) Identification of mortality risk factors; 3) Therapeutic strategies for decrease post-TX mortality and; 4) Prediction of mortality and ischaemic heart disease.

Supporting inquiry learning by promoting normative understanding of multivariable causality

NASA Astrophysics Data System (ADS)

Keselman, Alla

2003-11-01

Early adolescents may lack the cognitive and metacognitive skills necessary for effective inquiry learning. In particular, they are likely to have a nonnormative mental model of multivariable causality in which effects of individual variables are neither additive nor consistent. Described here is a software-based intervention designed to facilitate students' metalevel and performance-level inquiry skills by enhancing their understanding of multivariable causality. Relative to an exploration-only group, sixth graders who practiced predicting an outcome (earthquake risk) based on multiple factors demonstrated increased attention to evidence, improved metalevel appreciation of effective strategies, and a trend toward consistent use of a controlled comparison strategy. Sixth graders who also received explicit instruction in making predictions based on multiple factors showed additional improvement in their ability to compare multiple instances as a basis for inferences and constructed the most accurate knowledge of the system. Gains were maintained in transfer tasks. The cognitive skills and metalevel understanding examined here are essential to inquiry learning.

Adolescent Suicidal Behavior and Substance Use: Developmental Mechanisms

PubMed Central

Dawes, Michael A; Mathias, Charles W; Richard, Dawn M; Hill-Kapturczak, Nathalie; Dougherty, Donald M

2008-01-01

Adolescent suicidal behaviors and substance use are disturbingly common. Research suggests overlap of some of the etiological mechanisms for both adolescent suicidal behavior and substance use, yet clear understanding of the complex relations between these behaviors and their causal underpinnings is lacking. A growing body of evidence and a diathesis model (Mann et al. 1999; Mann, 2003) highlight the importance of impulse control as a proximal risk factor for adolescent suicidal and substance use behaviors. This literature review extends current theory on the relationships between adolescent suicidal behavior and substance use by: (1) examining how, when, and to what extent adolescent development is affected by poor impulse control, stressful life events, substance use behavior, and biological factors; (2) presenting proposed causal mechanisms by which these risk factors interact to increase risk for suicidal behaviors and substance use; and (3) proposing specific new hypotheses to extend the diathesis model to adolescents at risk for suicide and substance use. More specifically, new hypotheses are presented that predict bidirectional relationships between stressful life events and genetic markers of 5-HT dysregulation; substance use behavior and impulsivity; and substance use behavior and suicide attempts. The importance of distinguishing between different developmental trajectories of suicidal and substance use behaviors, and the effects of specific risk and protective mechanisms are discussed. Use of new statistical approaches that provide for the comparison of latent growth curves and latent class models is recommended to identify differences in developmental trajectories of suicidal behavior and substance use. Knowledge gained from these prospective longitudinal methods should lead to greater understanding on the timing, duration, and extent to which specific risk and protective factors influence the outcomes of suicidal behavior and substance use. In turn, findings from these studies should inform researchers who conduct future treatment and prevention studies. PMID:20651946

Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer.

PubMed

Painter, Jodie N; O'Mara, Tracy A; Marquart, Louise; Webb, Penelope M; Attia, John; Medland, Sarah E; Cheng, Timothy; Dennis, Joe; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley V; Beckmann, Matthias W; Ekici, Arif B; Fasching, Peter A; Hein, Alexander; Rübner, Matthias; Czene, Kamila; Darabi, Hatef; Hall, Per; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Amant, Frederic; Annibali, Daniela; Depreeuw, Jeroen; Lambrechts, Diether; Neven, Patrick; Cunningham, Julie M; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica M J; Ashton, Katie A; Otton, Geoffrey; Proietto, Anthony; Mints, Miriam; Tham, Emma; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Tomlinson, Ian; Dunning, Alison M; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

2016-11-01

The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls. Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 × 10 -17 ). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m 2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89-2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44-1.68, per 5 kg/m 2 ). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10-1.39; P = 5.3 × 10 -4 ). There was evidence of directional pleiotropy (P = 1.5 × 10 -4 ). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 × 10 -4 ), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS. BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503-10. ©2016 AACR. ©2016 American Association for Cancer Research.

A Children of Twins Study of parental divorce and offspring psychopathology

PubMed Central

D'Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Maes, Hermine H.; Silberg, Judy; Eaves, Lindon J.

2010-01-01

Background Although parental divorce is associated with increased substance use and internalizing problems, experiencing the separation of one's parents may not cause these outcomes. The relations may be due to genetic or environmental selection factors, characteristics that lead to both marital separation and offspring functioning. Method We used the Children of Twins (CoT) Design to explore whether unmeasured genetic or environmental factors related to the twin parent, and measured characteristics of both parents, account for the association between parental divorce and offspring substance use and internalizing problems. Results The association between parental divorce and offspring substance use problems remained robust when controlling for genetic and environmental risk from the twin parent associated with parental divorce, and measured characteristics of both parents. The results do not prove, but are consistent with, a causal connection. In contrast, the analyses suggest that shared genetic liability in parents and their offspring accounts for the increased risk of internalizing problems in adult offspring from divorced families. Conclusions The study illustrates that unmeasured genetic and environmental selection factors must be considered when studying parental divorce. In explaining associations between parental divorce and young-adult adjustment, our evidence suggests that selection versus causal mechanisms may operate differently for substance abuse (a causal relation) and internalizing problems (an artifact of selection). The CoT design only controls for the genetic and environmental characteristics of one parent; thus, additional genetically informed analyses are needed. PMID:17593147

Testing the Developmental Origins of Health and Disease Hypothesis for Psychopathology Using Family-Based Quasi-Experimental Designs

PubMed Central

D’Onofrio, Brian M.; Class, Quetzal A.; Lahey, Benjamin B.; Larsson, Henrik

2014-01-01

The Developmental Origin of Health and Disease (DOHaD) hypothesis is a broad theoretical framework that emphasizes how early risk factors have a causal influence on psychopathology. Researchers have raised concerns about the causal interpretation of statistical associations between early risk factors and later psychopathology because most existing studies have been unable to rule out the possibility of environmental and genetic confounding. In this paper we illustrate how family-based quasi-experimental designs can test the DOHaD hypothesis by ruling out alternative hypotheses. We review the logic underlying sibling-comparison, co-twin control, offspring of siblings/twins, adoption, and in vitro fertilization designs. We then present results from studies using these designs focused on broad indices of fetal development (low birth weight and gestational age) and a particular teratogen, smoking during pregnancy. The results provide mixed support for the DOHaD hypothesis for psychopathology, illustrating the critical need to use design features that rule out unmeasured confounding. PMID:25364377

How medicine has become a science?

PubMed

Zieliński, Andrzej

2014-01-01

The historical review of medical activities draws attention how late in its very long history therapies of proven effectiveness were introduced. Author attributes it to the late development of methods which would be capable to determine the causal relations which would scientifically justified identification the causes and risk factors of diseases as well as checking the effectiveness of preventive and therapeutic procedures. Among the fundamental tools for scientific knowledge of the causes and mechanisms of diseases, the author indicates: achievements of basic science and the development of epidemiological methods used to study causal relationships. In the author's opinion the results of basic research are an essential source of variables among which, with an increased likelihood could be found the causes and risk factors of studied conditions, including diseases. The author also stresses the role of medical technology, which is the primary source of potential medicines, other therapeutic procedures and diagnostic methods whose effectiveness is tested in experimental epidemiological studies. Medical technologies create also tools for the development of basic sciences.

Diagram-based Analysis of Causal Systems (DACS): elucidating inter-relationships between determinants of acute lower respiratory infections among children in sub-Saharan Africa.

PubMed

Rehfuess, Eva A; Best, Nicky; Briggs, David J; Joffe, Mike

2013-12-06

Effective interventions require evidence on how individual causal pathways jointly determine disease. Based on the concept of systems epidemiology, this paper develops Diagram-based Analysis of Causal Systems (DACS) as an approach to analyze complex systems, and applies it by examining the contributions of proximal and distal determinants of childhood acute lower respiratory infections (ALRI) in sub-Saharan Africa. Diagram-based Analysis of Causal Systems combines the use of causal diagrams with multiple routinely available data sources, using a variety of statistical techniques. In a step-by-step process, the causal diagram evolves from conceptual based on a priori knowledge and assumptions, through operational informed by data availability which then undergoes empirical testing, to integrated which synthesizes information from multiple datasets. In our application, we apply different regression techniques to Demographic and Health Survey (DHS) datasets for Benin, Ethiopia, Kenya and Namibia and a pooled World Health Survey (WHS) dataset for sixteen African countries. Explicit strategies are employed to make decisions transparent about the inclusion/omission of arrows, the sign and strength of the relationships and homogeneity/heterogeneity across settings.Findings about the current state of evidence on the complex web of socio-economic, environmental, behavioral and healthcare factors influencing childhood ALRI, based on DHS and WHS data, are summarized in an integrated causal diagram. Notably, solid fuel use is structured by socio-economic factors and increases the risk of childhood ALRI mortality. Diagram-based Analysis of Causal Systems is a means of organizing the current state of knowledge about a specific area of research, and a framework for integrating statistical analyses across a whole system. This partly a priori approach is explicit about causal assumptions guiding the analysis and about researcher judgment, and wrong assumptions can be reversed following empirical testing. This approach is well-suited to dealing with complex systems, in particular where data are scarce.

Diagram-based Analysis of Causal Systems (DACS): elucidating inter-relationships between determinants of acute lower respiratory infections among children in sub-Saharan Africa

PubMed Central

2013-01-01

Background Effective interventions require evidence on how individual causal pathways jointly determine disease. Based on the concept of systems epidemiology, this paper develops Diagram-based Analysis of Causal Systems (DACS) as an approach to analyze complex systems, and applies it by examining the contributions of proximal and distal determinants of childhood acute lower respiratory infections (ALRI) in sub-Saharan Africa. Results Diagram-based Analysis of Causal Systems combines the use of causal diagrams with multiple routinely available data sources, using a variety of statistical techniques. In a step-by-step process, the causal diagram evolves from conceptual based on a priori knowledge and assumptions, through operational informed by data availability which then undergoes empirical testing, to integrated which synthesizes information from multiple datasets. In our application, we apply different regression techniques to Demographic and Health Survey (DHS) datasets for Benin, Ethiopia, Kenya and Namibia and a pooled World Health Survey (WHS) dataset for sixteen African countries. Explicit strategies are employed to make decisions transparent about the inclusion/omission of arrows, the sign and strength of the relationships and homogeneity/heterogeneity across settings. Findings about the current state of evidence on the complex web of socio-economic, environmental, behavioral and healthcare factors influencing childhood ALRI, based on DHS and WHS data, are summarized in an integrated causal diagram. Notably, solid fuel use is structured by socio-economic factors and increases the risk of childhood ALRI mortality. Conclusions Diagram-based Analysis of Causal Systems is a means of organizing the current state of knowledge about a specific area of research, and a framework for integrating statistical analyses across a whole system. This partly a priori approach is explicit about causal assumptions guiding the analysis and about researcher judgment, and wrong assumptions can be reversed following empirical testing. This approach is well-suited to dealing with complex systems, in particular where data are scarce. PMID:24314302

Genetic causal beliefs about obesity, self-efficacy for weight control, and obesity-related behaviours in a middle-aged female cohort.

PubMed

Knerr, Sarah; Bowen, Deborah J; Beresford, Shirley A A; Wang, Catharine

2016-01-01

Obesity is a heritable condition with well-established risk-reducing behaviours. Studies have shown that beliefs about the causes of obesity are associated with diet and exercise behaviour. Identifying mechanisms linking causal beliefs and behaviours is important for obesity prevention and control. Cross-sectional multi-level regression analyses of self-efficacy for weight control as a possible mediator of obesity attributions (diet, physical activity, genetic) and preventive behaviours in 487 non-Hispanic White women from South King County, Washington. Self-reported daily fruit and vegetable intake and weekly leisure-time physical activity. Diet causal beliefs were positively associated with fruit and vegetable intake, with self-efficacy for weight control partially accounting for this association. Self-efficacy for weight control also indirectly linked physical activity attributions and physical activity behaviour. Relationships between genetic causal beliefs, self-efficacy for weight control, and obesity-related behaviours differed by obesity status. Self-efficacy for weight control contributed to negative associations between genetic causal attributions and obesity-related behaviours in non-obese, but not obese, women. Self-efficacy is an important construct to include in studies of genetic causal beliefs and behavioural self-regulation. Theoretical and longitudinal work is needed to clarify the causal nature of these relationships and other mediating and moderating factors.

Causal modelling applied to the risk assessment of a wastewater discharge.

PubMed

Paul, Warren L; Rokahr, Pat A; Webb, Jeff M; Rees, Gavin N; Clune, Tim S

2016-03-01

Bayesian networks (BNs), or causal Bayesian networks, have become quite popular in ecological risk assessment and natural resource management because of their utility as a communication and decision-support tool. Since their development in the field of artificial intelligence in the 1980s, however, Bayesian networks have evolved and merged with structural equation modelling (SEM). Unlike BNs, which are constrained to encode causal knowledge in conditional probability tables, SEMs encode this knowledge in structural equations, which is thought to be a more natural language for expressing causal information. This merger has clarified the causal content of SEMs and generalised the method such that it can now be performed using standard statistical techniques. As it was with BNs, the utility of this new generation of SEM in ecological risk assessment will need to be demonstrated with examples to foster an understanding and acceptance of the method. Here, we applied SEM to the risk assessment of a wastewater discharge to a stream, with a particular focus on the process of translating a causal diagram (conceptual model) into a statistical model which might then be used in the decision-making and evaluation stages of the risk assessment. The process of building and testing a spatial causal model is demonstrated using data from a spatial sampling design, and the implications of the resulting model are discussed in terms of the risk assessment. It is argued that a spatiotemporal causal model would have greater external validity than the spatial model, enabling broader generalisations to be made regarding the impact of a discharge, and greater value as a tool for evaluating the effects of potential treatment plant upgrades. Suggestions are made on how the causal model could be augmented to include temporal as well as spatial information, including suggestions for appropriate statistical models and analyses.

Drug and herb induced liver injury: Council for International Organizations of Medical Sciences scale for causality assessment

PubMed Central

Teschke, Rolf; Wolff, Albrecht; Frenzel, Christian; Schwarzenboeck, Alexander; Schulze, Johannes; Eickhoff, Axel

2014-01-01

Causality assessment of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences (CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment. The strength of the CIOMS lies in its potential as a standardized scale for DILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIOMS scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIOMS appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected DILI and HILI cases, applicable primarily at all assessing levels involved. PMID:24653791

A causal loop analysis of the sustainability of integrated community case management in Rwanda.

PubMed

Sarriot, Eric; Morrow, Melanie; Langston, Anne; Weiss, Jennifer; Landegger, Justine; Tsuma, Laban

2015-04-01

Expansion of community health services in Rwanda has come with the national scale up of integrated Community Case Management (iCCM) of malaria, pneumonia and diarrhea. We used a sustainability assessment framework as part of a large-scale project evaluation to identify factors affecting iCCM sustainability (2011). We then (2012) used causal-loop analysis to identify systems determinants of iCCM sustainability from a national systems perspective. This allows us to develop three high-probability future scenarios putting the achievements of community health at risk, and to recommend mitigating strategies. Our causal loop diagram highlights both balancing and reinforcing loops of cause and effect in the national iCCM system. Financial, political and technical scenarios carry high probability for threatening the sustainability through: (1) reduction in performance-based financing resources, (2) political shocks and erosion of political commitment for community health, and (3) insufficient progress in resolving district health systems--"building blocks"--performance gaps. In a complex health system, the consequences of choices may be delayed and hard to predict precisely. Causal loop analysis and scenario mapping make explicit complex cause-and-effects relationships and high probability risks, which need to be anticipated and mitigated. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Do cultural factors affect causal beliefs? Rational and magical thinking in Britain and Mexico.

PubMed

Subbotsky, Eugene; Quinteros, Graciela

2002-11-01

In two experiments, unusual phenomena (spontaneous destruction of objects in an empty wooden box) were demonstrated to adult participants living in rural communities in Mexico. These were accompanied by actions which had no physical link to the destroyed object but could suggest either scientifically based (the effect of an unknown physical device) or non-scientifically based (the effect of a 'magic spell') causal explanations of the event. The results were compared to the results of the matching two experiments from the earlier study made in Britain. The expectation that scientifically based explanations would prevail in British participants' judgments and behaviours, whereas Mexican participants would be more tolerant toward magical explanations, received only partial support. The prevalence of scientific explanations over magical explanations was evident in British participants' verbal judgments but not in Mexican participants' judgments. In their behavioural responses under the low-risk condition, British participants rejected magical explanations more frequently than did Mexican participants. However, when the risk of disregarding the possible causal effect of magic was increased, participants in both samples showed an equal degree of credulity in the possible effect of magic. The data are interpreted in terms of the relationships between scientific and 'folk' representations of causality and object permanence.

Practitioner Review: What have we learnt about the causes of ADHD?

PubMed Central

Thapar, Anita; Cooper, Miriam; Eyre, Olga; Langley, Kate

2013-01-01

Background Attention deficit hyperactivity disorder (ADHD) and its possible causes still attract controversy. Genes, pre and perinatal risks, psychosocial factors and environmental toxins have all been considered as potential risk factors. Method This review (focussing on literature published since 1997, selected from a search of PubMed) critically considers putative risk factors with a focus on genetics and selected environmental risks, examines their relationships with ADHD and discusses the likelihood that these risks are causal as well as some of the main implications. Results No single risk factor explains ADHD. Both inherited and noninherited factors contribute and their effects are interdependent. ADHD is familial and heritable. Research into the inherited and molecular genetic contributions to ADHD suggest an important overlap with other neurodevelopmental problems, notably, autism spectrum disorders. Having a biological relative with ADHD, large, rare copy number variants, some small effect size candidate gene variants, extreme early adversity, pre and postnatal exposure to lead and low birth weight/prematurity have been most consistently found as risk factors, but none are yet known to be definitely causal. There is a large literature documenting associations between ADHD and a wide variety of putative environmental risks that can, at present, only be regarded as correlates. Findings from research designs that go beyond simply testing for association are beginning to contest the robustness of some environmental exposures previously thought to be ADHD risk factors. Conclusions The genetic risks implicated in ADHD generally tend to have small effect sizes or be rare and often increase risk of many other types of psychopathology. Thus, they cannot be used for prediction, genetic testing or diagnostic purposes beyond what is predicted by a family history. There is a need to consider the possibility of parents and siblings being similarly affected and how this might impact on engagement with families, influence interventions and require integration with adult services. Genetic contributions to disorder do not necessarily mean that medications are the treatment of choice. We also consider how findings might influence the conceptualisation of ADHD, public health policy implications and why it is unhelpful and incorrect to dichotomise genetic/biological and environmental explanations. It is essential that practitioners can interpret genetic and aetiological research findings and impart informed explanations to families. PMID:22963644

Risk factors for testicular cancer: a case-control study in twins.

PubMed

Swerdlow, A J; De Stavola, B L; Swanwick, M A; Mangtani, P; Maconochie, N E

1999-06-01

Early life and anthropometric risk factors for testicular cancer were examined in a case-control study in England and Wales in which affected male twins were compared with their unaffected male co-twins. Questionnaire data was obtained for 60 twin pairs. Significantly raised risk of testicular cancer occurred in twins who had longer arms and legs than their co-twin. There was a significant excess of testicular cancer reported in non-twin brothers, as well as in twin brothers, of cases. Risk was also significantly raised in relation to cryptorchidism. The results on limb length suggest that factors, perhaps nutritional, affecting growth before puberty, may be causes of testicular cancer. The results on risk in brothers add to evidence of a large genetic component in aetiology of the tumour. The risk associated with cryptorchidism in the twins accords with the hypothesis that cryptorchidism is causally associated with testicular cancer because it is a cause of the malignancy, rather than because the same maternal factors experienced in utero cause both conditions.

Water quality and non-point sources of risk: the Jiulong River Watershed, P. R. of China.

PubMed

Zhang, Jingjing; Zhang, Luoping; Ricci, Paolo F

2012-01-01

Retrospective water quality assessment plays an essential role in identifying trends and causal associations between exposures and risks, thus it can be a guide for water resources management. We have developed empirical relationships between several time-varying social and economic factors of economic development, water quality variables such as nitrate-nitrogen, COD(Mn), BOD(5), and DO, in the Jiulong River Watershed and its main tributary, the West River. Our analyses used alternative statistical methods to reduce the dimensionality of the analysis first and then strengthen the study's causal associations. The statistical methods included: factor analysis (FA), trend analysis, Monte Carlo/bootstrap simulations, robust regressions and a coupled equations model, integrated into a framework that allows an investigation and resolution of the issues that may affect the estimated results. After resolving these, we found that the concentrations of nitrogen compounds increased over time in the West River region, and that fertilizer used in agricultural fruit crops was the main risk with regard to nitrogen pollution. The relationships we developed can identify hazards and explain the impact of sources of different types of pollution, such as urbanization, and agriculture.

Spatial distribution of a population at risk: an important factor for understanding the recent rise in tick-borne diseases (Lyme borreliosis and tick-borne encephalitis in the Czech Republic).

PubMed

Zeman, Petr; Benes, Cestmir

2013-12-01

Recent rise in tick-borne diseases in many parts of Europe is a phenomenon in need of an explanation. We analyzed temporal trends in spatial distribution of a population at risk of Lyme borreliosis, tick-borne encephalitis, and as a control, also of a 'non-tick-borne disease' in the Czech Republic in 1997-2010. Analysis revealed that the population's exposure had been increasingly confined to the nearest surroundings of residences or in totally residential locations and that the incidence of the diseases depended in some causal way on how close to residences people exposed themselves to the risk. The rise in Lyme borreliosis and tick-borne encephalitis was solely due to infections acquired at or near patients' homes (<5 km), while the number of cases acquired further away was decreasing. The detected patterns in the data question some of the hypotheses which may be applicable in explaining the rise in disease incidences in the Czech Republic including the effect of climate change. Potentially causal factors are discussed. Copyright © 2013 Elsevier GmbH. All rights reserved.

The social determinants of oral health: new approaches to conceptualizing and researching complex causal networks.

PubMed

Newton, J Timothy; Bower, Elizabeth J

2005-02-01

Oral epidemiological research into the social determinants of oral health has been limited by the absence of a theoretical framework which reflects the complexity of real life social processes and the network of causal pathways between social structure and oral health and disease. In the absence of such a framework, social determinants are treated as isolated risk factors, attributable to the individual, having a direct impact on oral health. There is little sense of how such factors interrelate over time and place and the pathways between the factors and oral health. Features of social life which impact on individuals' oral health but are not reducible to the individual remain under-researched. A conceptual framework informing mainstream epidemiological research into the social determinants of health is applied to oral epidemiology. The framework suggests complex causal pathways between social structure and health via interlinking material, psychosocial and behavioural pathways. Methodological implications for oral epidemiological research informed by the framework, such as the use of multilevel modelling, path analysis and structural equation modelling, combining qualitative and quantitative research methods, and collaborative research, are discussed. Copyright Blackwell Munksgaard, 2005.

DYNAMO-HIA--a Dynamic Modeling tool for generic Health Impact Assessments.

PubMed

Lhachimi, Stefan K; Nusselder, Wilma J; Smit, Henriette A; van Baal, Pieter; Baili, Paolo; Bennett, Kathleen; Fernández, Esteve; Kulik, Margarete C; Lobstein, Tim; Pomerleau, Joceline; Mackenbach, Johan P; Boshuizen, Hendriek C

2012-01-01

Currently, no standard tool is publicly available that allows researchers or policy-makers to quantify the impact of policies using epidemiological evidence within the causal framework of Health Impact Assessment (HIA). A standard tool should comply with three technical criteria (real-life population, dynamic projection, explicit risk-factor states) and three usability criteria (modest data requirements, rich model output, generally accessible) to be useful in the applied setting of HIA. With DYNAMO-HIA (Dynamic Modeling for Health Impact Assessment), we introduce such a generic software tool specifically designed to facilitate quantification in the assessment of the health impacts of policies. DYNAMO-HIA quantifies the impact of user-specified risk-factor changes on multiple diseases and in turn on overall population health, comparing one reference scenario with one or more intervention scenarios. The Markov-based modeling approach allows for explicit risk-factor states and simulation of a real-life population. A built-in parameter estimation module ensures that only standard population-level epidemiological evidence is required, i.e. data on incidence, prevalence, relative risks, and mortality. DYNAMO-HIA provides a rich output of summary measures--e.g. life expectancy and disease-free life expectancy--and detailed data--e.g. prevalences and mortality/survival rates--by age, sex, and risk-factor status over time. DYNAMO-HIA is controlled via a graphical user interface and is publicly available from the internet, ensuring general accessibility. We illustrate the use of DYNAMO-HIA with two example applications: a policy causing an overall increase in alcohol consumption and quantifying the disease-burden of smoking. By combining modest data needs with general accessibility and user friendliness within the causal framework of HIA, DYNAMO-HIA is a potential standard tool for health impact assessment based on epidemiologic evidence.

The complex spine: the multidimensional system of causal pathways for low-back disorders.

PubMed

Marras, William S

2012-12-01

The aim of this study was to examine the logic behind the knowledge of low-back problem causal pathways. Low-back pain and low-back disorders (LBDs) continue to represent the major musculoskeletal risk problem in the workplace,with the prevalence and costs of such disorders increasing over time. In recent years, there has been much criticism of the ability of ergonomics methods to control the risk of LBDs. Logical assessment of the systems logic associated with our understanding and prevention of LBDs. Current spine loading as well as spine tolerance research efforts are bringing the field to the point where there is a better systems understanding of the inextricable link between the musculoskeletal system and the cognitive system. Loading is influenced by both the physical environment factors as well as mental demands, whereas tolerances are defined by both physical tissue tolerance and biochemically based tissue sensitivities to pain. However, the logic used in many low-back risk assessment tools may be overly simplistic, given what is understood about causal pathways. Current tools typically assess only load or position in a very cursory manner. Efforts must work toward satisfying both the physical environment and the cognitive environment for the worker if one is to reliably lower the risk of low-back problems. This systems representation of LBD development may serve as a guide to identify gaps in our understanding of LBDs.

Crash causal factors and countermeasures for high-risk locations on multilane primary highways in Virginia.

DOT National Transportation Integrated Search

2009-01-01

In 2004, a total of 95,020 vehicle crashes occurred on highways under the jurisdiction of the Virginia Department of Transportation (VDOT). Of these, 39,847 crashes occurred on primary highways, and 345 of these were fatal crashes. VDOT's traffic eng...

(n-3) Fatty acids alleviate adipose tissue inflammation and insulin resistance: Mechanistic insights

USDA-ARS?s Scientific Manuscript database

Obesity is associated with the metabolic syndrome, a significant risk factor for developing type-2 diabetes and cardiovascular diseases. A chronic low-grade inflammation occurring in the adipose tissue of obese individuals is causally linked to the pathogenesis of insulin resistance and the metaboli...

Overexpression of the Cytokine BAFF and Autoimmunity Risk.

PubMed

Steri, Maristella; Orrù, Valeria; Idda, M Laura; Pitzalis, Maristella; Pala, Mauro; Zara, Ilenia; Sidore, Carlo; Faà, Valeria; Floris, Matteo; Deiana, Manila; Asunis, Isadora; Porcu, Eleonora; Mulas, Antonella; Piras, Maria G; Lobina, Monia; Lai, Sandra; Marongiu, Mara; Serra, Valentina; Marongiu, Michele; Sole, Gabriella; Busonero, Fabio; Maschio, Andrea; Cusano, Roberto; Cuccuru, Gianmauro; Deidda, Francesca; Poddie, Fausto; Farina, Gabriele; Dei, Mariano; Virdis, Francesca; Olla, Stefania; Satta, Maria A; Pani, Mario; Delitala, Alessandro; Cocco, Eleonora; Frau, Jessica; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Ferrigno, Paola; Ban, Maria; Barizzone, Nadia; Leone, Maurizio; Guerini, Franca R; Piga, Matteo; Firinu, Davide; Kockum, Ingrid; Lima Bomfim, Izaura; Olsson, Tomas; Alfredsson, Lars; Suarez, Ana; Carreira, Patricia E; Castillo-Palma, Maria J; Marcus, Joseph H; Congia, Mauro; Angius, Andrea; Melis, Maurizio; Gonzalez, Antonio; Alarcón Riquelme, Marta E; da Silva, Berta M; Marchini, Maurizio; Danieli, Maria G; Del Giacco, Stefano; Mathieu, Alessandro; Pani, Antonello; Montgomery, Stephen B; Rosati, Giulio; Hillert, Jan; Sawcer, Stephen; D'Alfonso, Sandra; Todd, John A; Novembre, John; Abecasis, Gonçalo R; Whalen, Michael B; Marrosu, Maria G; Meloni, Alessandra; Sanna, Serena; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco

2017-04-27

Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).

Time-varying causal network of the Korean financial system based on firm-specific risk premiums

NASA Astrophysics Data System (ADS)

Song, Jae Wook; Ko, Bonggyun; Cho, Poongjin; Chang, Woojin

2016-09-01

The aim of this paper is to investigate the Korean financial system based on time-varying causal network. We discover many stylized facts by utilizing the firm-specific risk premiums for measuring the causality direction from a firm to firm. At first, we discover that the interconnectedness of causal network is affected by the outbreak of financial events; the co-movement of firm-specific risk premium is strengthened after each positive event, and vice versa. Secondly, we find that the major sector of the Korean financial system is the Depositories, and the financial reform in June-2011 achieves its purpose by weakening the power of risk-spillovers of Broker-Dealers. Thirdly, we identify that the causal network is a small-world network with scale-free topology where the power-law exponents of out-Degree and negative event are more significant than those of in-Degree and positive event. Lastly, we discuss that the current aspects of causal network are closely related to the long-term future scenario of the KOSPI Composite index where the direction and stability are significantly affected by the power of risk-spillovers and the power-law exponents of degree distributions, respectively.

Modelling runway incursion severity.

PubMed

Wilke, Sabine; Majumdar, Arnab; Ochieng, Washington Y

2015-06-01

Analysis of the causes underlying runway incursions is fundamental for the development of effective mitigation measures. However, there are significant weaknesses in the current methods to model these factors. This paper proposes a structured framework for modelling causal factors and their relationship to severity, which includes a description of the airport surface system architecture, establishment of terminological definitions, the determination and collection of appropriate data, the analysis of occurrences for severity and causes, and the execution of a statistical analysis framework. It is implemented in the context of U.S. airports, enabling the identification of a number of priority interventions, including the need for better investigation and causal factor capture, recommendations for airfield design, operating scenarios and technologies, and better training for human operators in the system. The framework is recommended for the analysis of runway incursions to support safety improvements and the methodology is transferable to other areas of aviation safety risk analysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Maternal obesity and childhood wheezing and asthma.

PubMed

Rusconi, Franca; Popovic, Maja

2017-03-01

Obesity represents one of the major public health problems worldwide, with an increased prevalence also among women of reproductive age. Maternal pre-pregnancy overweight and obesity are important risk factors for a number of maternal and foetal/neonatal complications. The objective of this review is to provide an overview of the most recent evidence regarding the associations between pre-pregnancy overweight/obesity and wheezing and asthma in childhood. Potential mechanisms, mediators and confounding factors involved in these associations are also discussed. Despite the relatively large body of studies examining these associations and taking into account main confounders and potential mediators, the causal relationship between maternal obesity and wheezing and asthma in childhood is still uncertain. This uncertainty is not trivial, as any prevention strategy aimed at reducing the burden of these conditions would necessarily imply better understanding of the factors that are in the causal chain. Copyright © 2016. Published by Elsevier Ltd.

The impact of airport characteristics on airport surface accidents and incidents.

PubMed

Wilke, Sabine; Majumdar, Arnab; Ochieng, Washington Y

2015-06-01

Airport surface safety and in particular runway and taxiway safety is acknowledged globally as one of aviation's greatest challenges. To improve this key area of aviation safety, it is necessary to identify and understand the causal and contributing factors on safety occurrences. While the contribution of human factors, operations, and procedures has been researched extensively, the impact of the airport and its associated characteristics itself has received little or no attention. This paper introduces a novel methodology for risk and hazard assessment of airport surface operations, and models the relationships between airport characteristics, and (a) the rate of occurrences, (b) the severity of occurrences, and (c) the causal factors underlying occurrences. The results show for the first time how the characteristics of airports, and in particular its infrastructure and operations, influence the safety of surface operations. Copyright © 2015 Elsevier Ltd. and National Safety Council. Published by Elsevier Ltd. All rights reserved.

Genome-wide association analysis and replication of coronary artery disease in South Korea suggests a causal variant common to diverse populations

PubMed Central

Cho, Eun Young; Jang, Yangsoo; Shin, Eun Soon; Jang, Hye Yoon; Yoo, Yeon-Kyeong; Kim, Sook; Jang, Ji Hyun; Lee, Ji Yeon; Yun, Min Hye; Park, Min Young; Chae, Jey Sook; Lim, Jin Woo; Shin, Dong Jik; Park, Sungha; Lee, Jong Ho; Han, Bok Ghee; Rae, Kim Hyung; Cardon, Lon R; Morris, Andrew P; Lee, Jong Eun; Clarke, Geraldine M

2010-01-01

Background Recent genome-wide association (GWA) studies have identified and replicated several genetic loci associated with the risk of development of coronary artery disease (CAD) in samples from populations of Caucasian and Asian descent. However, only chromosome 9p21 has been confirmed as a major susceptibility locus conferring risk for development of CAD across multiple ethnic groups. The authors aimed to find evidence of further similarities and differences in genetic risk of CAD between Korean and other populations. Methods The authors performed a GWA study comprising 230 cases and 290 controls from a Korean population typed on 490 032 single nucleotide polymorphisms (SNPs). A total of 3148 SNPs were taken forward for genotyping in a subsequent replication study using an independent sample of 1172 cases and 1087 controls from the same population. Results The association previously observed on chromosome 9p21 was independently replicated (p=3.08e–07). Within this region, the same risk haplotype was observed in samples from both Korea and of Western European descent, suggesting that the causal mutation carried on this background occurred on a single ancestral allele. Other than 9p21, the authors were unable to replicate any of the previously reported signals for association with CAD. Furthermore, no evidence of association was found at chromosome 1q41 for risk of myocardial infarction, previously identified as conferring risk in a Japanese population. Conclusion A common causal variant is likely to be responsible for risk of CAD in Korean and Western European populations at chromosome 9p21.3. Further investigations are required to confirm non-replication of any other cross-race genetic risk factors. PMID:27325954

Associations between Potentially Modifiable Risk Factors and Alzheimer Disease: A Mendelian Randomization Study

PubMed Central

Østergaard, Søren D.; Mukherjee, Shubhabrata; Sharp, Stephen J.; Proitsi, Petroula; Lotta, Luca A.; Day, Felix; Perry, John R. B.; Boehme, Kevin L.; Walter, Stefan; Kauwe, John S.; Gibbons, Laura E.; Larson, Eric B.; Powell, John F.; Langenberg, Claudia; Crane, Paul K.; Wareham, Nicholas J.; Scott, Robert A.

2015-01-01

Background Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer disease (AD) and represent promising targets for intervention. However, the causality of these associations is unclear. We sought to assess the causal nature of these associations using Mendelian randomization (MR). Methods and Findings We used SNPs associated with each risk factor as instrumental variables in MR analyses. We considered type 2 diabetes (T2D, N SNPs = 49), fasting glucose (N SNPs = 36), insulin resistance (N SNPs = 10), body mass index (BMI, N SNPs = 32), total cholesterol (N SNPs = 73), HDL-cholesterol (N SNPs = 71), LDL-cholesterol (N SNPs = 57), triglycerides (N SNPs = 39), systolic blood pressure (SBP, N SNPs = 24), smoking initiation (N SNPs = 1), smoking quantity (N SNPs = 3), university completion (N SNPs = 2), and years of education (N SNPs = 1). We calculated MR estimates of associations between each exposure and AD risk using an inverse-variance weighted approach, with summary statistics of SNP–AD associations from the International Genomics of Alzheimer’s Project, comprising a total of 17,008 individuals with AD and 37,154 cognitively normal elderly controls. We found that genetically predicted higher SBP was associated with lower AD risk (odds ratio [OR] per standard deviation [15.4 mm Hg] of SBP [95% CI]: 0.75 [0.62–0.91]; p = 3.4 × 10−3). Genetically predicted higher SBP was also associated with a higher probability of taking antihypertensive medication (p = 6.7 × 10−8). Genetically predicted smoking quantity was associated with lower AD risk (OR per ten cigarettes per day [95% CI]: 0.67 [0.51–0.89]; p = 6.5 × 10−3), although we were unable to stratify by smoking history; genetically predicted smoking initiation was not associated with AD risk (OR = 0.70 [0.37, 1.33]; p = 0.28). We saw no evidence of causal associations between glycemic traits, T2D, BMI, or educational attainment and risk of AD (all p > 0.1). Potential limitations of this study include the small proportion of intermediate trait variance explained by genetic variants and other implicit limitations of MR analyses. Conclusions Inherited lifetime exposure to higher SBP is associated with lower AD risk. These findings suggest that higher blood pressure—or some environmental exposure associated with higher blood pressure, such as use of antihypertensive medications—may reduce AD risk. PMID:26079503

Commentary: How can family-based quasi-experimental designs and national registers be used to address confounding in risk factor studies of psychopathology? A reflection on Obel et al. (2016).

PubMed

Larsson, Henrik

2016-04-01

Standard observational studies have reported a robust correlation between maternal smoking during pregnancy and risk of ADHD in offspring. In the accompanying article, Obel et al. used sibling-comparisons to explore the extent to which unmeasured familial confounding explains this association. This commentary highlights three important implications of the study. At a general level, Obel et al. illustrates how (1) family-based quasi-experimental designs and (2) national registers can be used to address confounding in risk factor studies of psychopathology. At a more specific level, the study suggests that maternal smoking during pregnancy is probably not a causal risk factor for ADHD. © 2016 Association for Child and Adolescent Mental Health.

Health Implications of High-Fructose Intake and Current Research12

PubMed Central

Dornas, Waleska C; de Lima, Wanderson G; Pedrosa, Maria L; Silva, Marcelo E

2015-01-01

Although fructose consumption has dramatically increased and is suspected to be causally linked to metabolic abnormalities, the mechanisms involved are still only partially understood. We discuss the available data and investigate the effects of dietary fructose on risk factors associated with metabolic disorders. The evidence suggests that fructose may be a predisposing cause in the development of insulin resistance in association with the induction of hypertriglyceridemia. Experiments in animals have shown this relation when they are fed diets very high in fructose or sucrose, and human studies also show this relation, although with conflicting results due to the heterogeneity of the studies. The link between increased fructose consumption and increases in uric acid also has been confirmed as a potential risk factor for metabolic syndrome, and insulin resistance/hyperinsulinemia may be causally related to the development of hypertension. Collectively, these results suggest a link between high fructose intake and insulin resistance, although future studies must be of reasonable duration, use defined populations, and improve comparisons regarding the effects of relevant doses of nutrients on specific endpoints to fully understand the effect of fructose intake in the absence of potential confounding factors. PMID:26567197

Molecular epidemiology of acute leukemia in children: causal model, interaction of three factors-susceptibility, environmental exposure and vulnerability period.

PubMed

Mejía-Aranguré, Juan Manuel

Acute leukemias have a huge morphological, cytogenetic and molecular heterogeneity and genetic polymorphisms associated with susceptibility. Every leukemia presents causal factors associated with the development of the disease. Particularly, when three factors are present, they result in the development of acute leukemia. These phenomena are susceptibility, environmental exposure and a period that, for this model, has been called the period of vulnerability. This framework shows how the concepts of molecular epidemiology have established a reference from which it is more feasible to identify the environmental factors associated with the development of leukemia in children. Subsequently, the arguments show that only susceptible children are likely to develop leukemia once exposed to an environmental factor. For additional exposure, if the child is not susceptible to leukemia, the disease does not develop. In addition, this exposure should occur during a time window when hematopoietic cells and their environment are more vulnerable to such interaction, causing the development of leukemia. This model seeks to predict the time when the leukemia develops and attempts to give a context in which the causality of childhood leukemia should be studied. This information can influence and reduce the risk of a child developing leukemia. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Multiple mechanisms influencing the relationship between alcohol consumption and peer alcohol use.

PubMed

Edwards, Alexis C; Maes, Hermine H; Prescott, Carol A; Kendler, Kenneth S

2015-02-01

Alcohol consumption is typically correlated with the alcohol use behaviors of one's peers. Previous research has suggested that this positive relationship could be due to social selection, social influence, or a combination of both processes. However, few studies have considered the role of shared genetic and environmental influences in conjunction with causal processes. This study uses data from a sample of male twins (N = 1,790) who provided retrospective reports of their own alcohol consumption and their peers' alcohol-related behaviors, from adolescence into young adulthood (ages 12 to 25). Structural equation modeling was employed to compare 3 plausible models of genetic and environmental influences on the relationship between phenotypes over time. Model fitting indicated that one's own alcohol consumption and the alcohol use of one's peers are related through both genetic and shared environmental factors and through unique environmental causal influences. The relative magnitude of these factors, and their contribution to covariation, changed over time, with genetic factors becoming more meaningful later in development. Peers' alcohol use behaviors and one's own alcohol consumption are related through a complex combination of genetic and environmental factors that act via correlated factors and the complementary causal mechanisms of social selection and influence. Understanding these processes can inform risk assessment as well as improve our ability to model the development of alcohol use. Copyright © 2015 by the Research Society on Alcoholism.

Multiple mechanisms influencing the relationship between alcohol consumption and peer alcohol use

PubMed Central

Edwards, Alexis C.; Maesr, Hermine H.; Prescott, Carol A.; Kendler, Kenneth S.

2014-01-01

Background Alcohol consumption is typically correlated with the alcohol use behaviors of one’s peers. Previous research has suggested that this positive relationship could be due to social selection, social influence, or a combination of both processes. However, few studies have considered the role of shared genetic and environmental influences in conjunction with causal processes. Methods The current study uses data from a sample of male twins (N=1790) who provided retrospective reports of their own alcohol consumption and their peers’ alcohol related behaviors, from adolescence into young adulthood (ages 12–25). Structural equation modeling was employed to compare three plausible models of genetic and environmental influences on the relationship between phenotypes over time. Results Model fitting indicated that one’s own alcohol consumption and the alcohol use of one’s peers are related through both genetic and shared environmental factors and through unique environmental causal influences. The relative magnitude of these factors, and their contribution to covariation, changed over time, with genetic factors becoming more meaningful later in development. Conclusions Peers’ alcohol use behaviors and one’s own alcohol consumption are related through a complex combination of genetic and environmental factors that act via correlated factors and the complementary causal mechanisms of social selection and influence. Understanding these processes can inform risk assessment as well as improve our ability to model the development of alcohol use. PMID:25597346

Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.

PubMed

Bonilla, Carolina; Lewis, Sarah J; Rowlands, Mari-Anne; Gaunt, Tom R; Davey Smith, George; Gunnell, David; Palmer, Tom; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Grönberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Lathrop, Mark; Martin, Richard M; Holly, Jeff M P

2016-10-01

Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. © 2016 UICC.

Outbreak of sudden cardiac deaths in a tire manufacturing facility: can it be caused by nanoparticles?

PubMed

Kim, Eun-A; Park, Jungsun; Kim, Kun-Hyung; Lee, Naroo; Kim, Dae-Seong; Kang, Seong-Kyu

2012-03-01

The purpose of this study was to review clinical characteristics and working environments of sudden cardiac death (SCD) cases associated with a tire manufacturer in Korea, and review possible occupational risk factors for cardiovascular disease including nanoparticles (ultrafine particles, UFPs). We reviewed (i) the clinical course of SCD cases and (ii) occupational and non-occupational risk factors including chemicals, the physical work environment, and job characteristics. Possible occupational factors were chemicals, UFPs of rubber fume, a hot environment, shift work, overworking, and noise exposure. The mean diameter of rubber fume (63-73 nm) was (larger than diesel exhaust [12 nm] and outdoor dust [50 nm]). The concentration of carbon disulfide, carbon monoxide and styrene were lower than the limit of detection. Five SCD cases were exposed to shift work and overworking. Most of the cases had several non-occupational factors such as hypertension, overweight and smoking. The diameter of rubber fume was larger than outdoor and the diesel exhaust, the most well known particulate having a causal relationship with cardiovascular disease. The possibility of a causal relation between UFPs of rubber fume and SCD was not supported in this study. However, it is necessary to continue studying the relationship between large sized UFPs and SCD.

Outbreak of Sudden Cardiac Deaths in a Tire Manufacturing Facility: Can It Be Caused by Nanoparticles?

PubMed Central

Kim, Eun-A; Kim, Kun-Hyung; Lee, Naroo; Kim, Dae-Seong; Kang, Seong-Kyu

2012-01-01

Objectives The purpose of this study was to review clinical characteristics and working environments of sudden cardiac death (SCD) cases associated with a tire manufacturer in Korea, and review possible occupational risk factors for cardiovascular disease including nanoparticles (ultrafine particles, UFPs). Methods We reviewed (i) the clinical course of SCD cases and (ii) occupational and non-occupational risk factors including chemicals, the physical work environment, and job characteristics. Results Possible occupational factors were chemicals, UFPs of rubber fume, a hot environment, shift work, overworking, and noise exposure. The mean diameter of rubber fume (63-73 nm) was (larger than diesel exhaust [12 nm] and outdoor dust [50 nm]). The concentration of carbon disulfide, carbon monoxide and styrene were lower than the limit of detection. Five SCD cases were exposed to shift work and overworking. Most of the cases had several non-occupational factors such as hypertension, overweight and smoking. Conclusion The diameter of rubber fume was larger than outdoor and the diesel exhaust, the most well known particulate having a causal relationship with cardiovascular disease. The possibility of a causal relation between UFPs of rubber fume and SCD was not supported in this study. However, it is necessary to continue studying the relationship between large sized UFPs and SCD. PMID:22953232

Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease

PubMed Central

Toth, Peter P

2016-01-01

Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant’s effect on TG levels correlating with the magnitude of the variant’s effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the available epidemiological, clinical, and genetic evidence relating to the atherogenicity of TRLs and their role in the progression of CVD. PMID:27226718

Investigating causality in the association between 25(OH)D and schizophrenia.

PubMed

Taylor, Amy E; Burgess, Stephen; Ware, Jennifer J; Gage, Suzanne H; Richards, J Brent; Davey Smith, George; Munafò, Marcus R

2016-05-24

Vitamin D deficiency is associated with increased risk of schizophrenia. However, it is not known whether this association is causal or what the direction of causality is. We performed two sample bidirectional Mendelian randomization analysis using single nucleotide polymorphisms (SNPs) robustly associated with serum 25(OH)D to investigate the causal effect of 25(OH)D on risk of schizophrenia, and SNPs robustly associated with schizophrenia to investigate the causal effect of schizophrenia on 25(OH)D. We used summary data from genome-wide association studies and meta-analyses of schizophrenia and 25(OH)D to obtain betas and standard errors for the SNP-exposure and SNP-outcome associations. These were combined using inverse variance weighted fixed effects meta-analyses. In 34,241 schizophrenia cases and 45,604 controls, there was no clear evidence for a causal effect of 25(OH)D on schizophrenia risk. The odds ratio for schizophrenia per 10% increase in 25(OH)D conferred by the four 25(OH)D increasing SNPs was 0.992 (95% CI: 0.969 to 1.015). In up to 16,125 individuals with measured serum 25(OH)D, there was no clear evidence that genetic risk for schizophrenia causally lowers serum 25(OH)D. These findings suggest that associations between schizophrenia and serum 25(OH)D may not be causal. Therefore, vitamin D supplementation may not prevent schizophrenia.

Causation in risk assessment and management: models, inference, biases, and a microbial risk-benefit case study.

PubMed

Cox, L A; Ricci, P F

2005-04-01

Causal inference of exposure-response relations from data is a challenging aspect of risk assessment with important implications for public and private risk management. Such inference, which is fundamentally empirical and based on exposure (or dose)-response models, seldom arises from a single set of data; rather, it requires integrating heterogeneous information from diverse sources and disciplines including epidemiology, toxicology, and cell and molecular biology. The causal aspects we discuss focus on these three aspects: drawing sound inferences about causal relations from one or more observational studies; addressing and resolving biases that can affect a single multivariate empirical exposure-response study; and applying the results from these considerations to the microbiological risk management of human health risks and benefits of a ban on antibiotic use in animals, in the context of banning enrofloxacin or macrolides, antibiotics used against bacterial illnesses in poultry, and the effects of such bans on changing the risk of human food-borne campylobacteriosis infections. The purposes of this paper are to describe novel causal methods for assessing empirical causation and inference; exemplify how to deal with biases that routinely arise in multivariate exposure- or dose-response modeling; and provide a simplified discussion of a case study of causal inference using microbial risk analysis as an example. The case study supports the conclusion that the human health benefits from a ban are unlikely to be greater than the excess human health risks that it could create, even when accounting for uncertainty. We conclude that quantitative causal analysis of risks is a preferable to qualitative assessments because it does not involve unjustified loss of information and is sound under the inferential use of risk results by management.

Genetic causal beliefs about obesity, self-efficacy for weight control, and obesity-related behaviours in a middle-aged female cohort

PubMed Central

Knerr, Sarah; Bowen, Deborah J.; Beresford, Shirley A.A.; Wang, Catharine

2015-01-01

Objective Obesity is a heritable condition with well-established risk-reducing behaviours. Studies have shown that beliefs about the causes of obesity are associated with diet and exercise behaviour. Identifying mechanisms linking causal beliefs and behaviours is important for obesity prevention and control. Design Cross-sectional multi-level regression analyses of self-efficacy for weight control as a possible mediator of obesity attributions (diet, physical activity, genetic) and preventive behaviours in 487 non-Hispanic White women from South King County, Washington. Main Outcome Measures Self-reported daily fruit and vegetable intake and weekly leisure-time physical activity. Results Diet causal beliefs were positively associated with fruit and vegetable intake, with self-efficacy for weight control partially accounting for this association. Self-efficacy for weight control also indirectly linked physical activity attributions and physical activity behaviour. Relationships between genetic causal beliefs, self-efficacy for weight control, and obesity-related behaviours differed by obesity status. Self-efficacy for weight control contributed to negative associations between genetic causal attributions and obesity-related behaviours in non-obese, but not obese, women. Conclusion Self-efficacy is an important construct to include in studies of genetic causal beliefs and behavioural self-regulation. Theoretical and longitudinal work is needed to clarify the causal nature of these relationships and other mediating and moderating factors. PMID:26542069

Mapping historical information for better understanding the causality factors of past disasters

NASA Astrophysics Data System (ADS)

Boudou, Martin; Lang, Michel; Vinet, Freddy; Coeur, Denis

2015-04-01

The Flood Directive of 2007 promotes the use of historical information in order to mitigate the impact of future extreme events. According to this text, the study of past events offers new insights for better understanding the causality factors of a disaster, from hydrometeorological keys to socio-political repercussions of the flood. In this presentation we decided to focus on the study of factors leading to the exceptionality of a hydrological flood event. This aspect is regularly pointed out by the feedbacks carried out after a catastrophic event and remains a subject of debate for risk managers. The role of antecedent meteorological conditions is especially underestimated by local authorities. These factors can however be considered as a key issue to appreciate the exceptional character of a hydrological disaster. For example the 2013 June floods in France that affected the region of Pyrenees revealed the significant contribution of snow melting to the discharges recorded. In an article of 2014, Schröter et al. showed that the soil moisture can be considered as a key driver of the generalised flood hazard intensity that affected Germany over the same month of June 2013. With regard to these assessments, some considerations emerge. Does a diachronic appraisal of past disasters point out the main issues responsible for an exceptional flood hazard level? Is there common causality issues involved into these extreme hydrological events? In order to answer these questions this presentation proposes a comparative analysis of nine major floods that impacted the French territory during the XXth century (from 1910 to 2010). The set is composed by different flood typologies (from torrential events to floods resulting from groundwater level rising) so as to get a complete view of flood risk in France. The methodology proposed relies on a cartographic approach to highlight the causality factors of these past hydrological disasters. For instance, mapping the rainfall data over the representation of the maximum discharges recorded can help to understand the significance of the rainfall event. In some cases, the use of textual historical information allows to emphasize the significance of other factors such as snow melting or the influence of anthropogenic infrastructures. Indeed, mapping historical information seems to be an original approach to represent the various spatial and temporal scales of historical disasters and an interesting tool to explore the exceptionality of the hazard level.

Inability to activate Rac1-dependent forgetting contributes to behavioral inflexibility in mutants of multiple autism-risk genes

PubMed Central

Dong, Tao; He, Jing; Wang, Shiqing; Wang, Lianzhang; Cheng, Yuqi; Zhong, Yi

2016-01-01

The etiology of autism is so complicated because it involves the effects of variants of several hundred risk genes along with the contribution of environmental factors. Therefore, it has been challenging to identify the causal paths that lead to the core autistic symptoms such as social deficit, repetitive behaviors, and behavioral inflexibility. As an alternative approach, extensive efforts have been devoted to identifying the convergence of the targets and functions of the autism-risk genes to facilitate mapping out causal paths. In this study, we used a reversal-learning task to measure behavioral flexibility in Drosophila and determined the effects of loss-of-function mutations in multiple autism-risk gene homologs in flies. Mutations of five autism-risk genes with diversified molecular functions all led to a similar phenotype of behavioral inflexibility indicated by impaired reversal-learning. These reversal-learning defects resulted from the inability to forget or rather, specifically, to activate Rac1 (Ras-related C3 botulinum toxin substrate 1)-dependent forgetting. Thus, behavior-evoked activation of Rac1-dependent forgetting has a converging function for autism-risk genes. PMID:27335463

Do Selective Serotonin Reuptake Inhibitors (SSRIs) Cause Fractures?

PubMed

Warden, Stuart J; Fuchs, Robyn K

2016-10-01

Recent meta-analyses report a 70 % increase in fracture risk in selective serotonin reuptake inhibitor (SSRI) users compared to non-users; however, included studies were observational and limited in their ability to establish causality. Here, we use the Bradford Hill criteria to explore causality between SSRIs and fractures. We found a strong, consistent, and temporal relationship between SSRIs and fractures, which appears to follow a biological gradient. However, specificity and biological plausibility remain concerns. In terms of specificity, the majority of available data have limitations due to either confounding by indication or channeling bias. Self-controlled case series address some of these limitations and provide relatively strong observational evidence for a causal relationship between SSRIs and fracture. In doing so, they suggest that falls contribute to fractures in SSRI users. Whether there are also underlying changes in skeletal properties remains unresolved. Initial studies provide some evidence for skeletal effects of SSRIs; however, the pathways involved need to be established before biological plausibility can be accepted. As the link between SSRIs and fractures is based on observational data and not evidence from prospective trials, there is insufficient evidence to definitively determine a causal relationship and it appears premature to label SSRIs as a secondary cause of osteoporosis. SSRIs appear to contribute to fracture-inducing falls, and addressing any fall risk associated with SSRIs may be an efficient approach to reducing SSRI-related fractures. As fractures stemming from SSRI-induced falls are more likely in individuals with compromised bone health, it is worth considering bone density testing and intervention for those presenting with risk factors for osteoporosis.

Antepartum risk factors for newborn encephalopathy: the Western Australian case-control study

PubMed Central

Badawi, Nadia; Kurinczuk, Jennifer J; Keogh, John M; Alessandri, Louisa M; O’Sullivan, Fiona; Burton, Paul R; Pemberton, Patrick J; Stanley, Fiona J

1998-01-01

Objective To ascertain antepartum predictors of newborn encephalopathy in term infants. Design Population based, unmatched case-control study. Setting Metropolitan area of Western Australia, June 1993 to September 1995. Subjects All 164 term infants with moderate or severe newborn encephalopathy; 400 randomly selected controls. Main outcome measures Adjusted odds ratio estimates. Results The birth prevalence of moderate or severe newborn encephalopathy was 3.8/1000 term live births. The neonatal fatality was 9.1%. The risk of newborn encephalopathy increased with increasing maternal age and decreased with increasing parity. There was an increased risk associated with having a mother who was unemployed (odds ratio 3.60), an unskilled manual worker (3.84), or a housewife (2.48). Other risk factors from before conception were not having private health insurance (3.46), a family history of seizures (2.55), a family history of neurological disease (2.73), and infertility treatment (4.43). Risk factors during pregnancy were maternal thyroid disease (9.7), severe pre-eclampsia (6.30), moderate or severe bleeding (3.57), a clinically diagnosed viral illness (2.97), not having drunk alcohol (2.91); and placenta described at delivery as abnormal (2.07). Factors related to the baby were birth weight adjusted for gestational age between the third and ninth centile (4.37) or below the third centile (38.23). The risk relation with gestational age was J shaped with 38 and 39 weeks having the lowest risk. Conclusions The causes of newborn encephalopathy are heterogeneous and many of the causal pathways start before birth. Key messagesThe birth prevalence of moderate or severe newborn encephalopathy was 3.8 per 1000 term live births and the neonatal case fatality was 9.1%Independent risk factors before conception and in the antepartum period for newborn encephalopathy include socioeconomic status, family history of seizures or other neurological disease, conception after infertility treatment, maternal thyroid disease, severe pre-eclampsia, bleeding in pregnancy, viral illness, having an abnormal placenta, intrauterine growth restriction, and postmaturityThe causes of newborn encephalopathy are heterogeneous and many causal pathways start in the antepartum period PMID:9836652

Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study

PubMed Central

Carreras-Torres, Robert; Johansson, Mattias; Haycock, Philip C.; Wade, Kaitlin H.; Relton, Caroline L.; Martin, Richard M.; Davey Smith, George; Albanes, Demetrius; Aldrich, Melinda C.; Andrew, Angeline; Bickeböller, Heike; Bojesen, Stig E.; Brunnström, Hans; Manjer, Jonas; Brüske, Irene; Caporaso, Neil E.; Chen, Chu; Christiani, David C.; Christian, W. Jay; Doherty, Jennifer A.; Duell, Eric J.; Goodman, Gary E.; Grankvist, Kjell; Haugen, Aage; Hong, Yun-Chul; Johansson, Mikael B.; Lam, Stephen; Landi, Maria Teresa; Lazarus, Philip; Le Marchand, Loïc; Liu, Geoffrey; Melander, Olle; Rennert, Gad; Risch, Angela; Haura, Eric B.; Scelo, Ghislaine; Zaridze, David; Mukeriya, Anush; Savić, Milan; Lissowska, Jolanta; Swiatkowska, Beata; Janout, Vladimir; Holcatova, Ivana; Mates, Dana; Shen, Hongbing; Tardon, Adonina; Woll, Penella; Tsao, Ming-Sound; Wu, Xifeng; Yuan, Jian-Min; Hung, Rayjean J.; Amos, Christopher I.; Brennan, Paul

2017-01-01

Background Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01–1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15–2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79–1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84–0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25–2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior. PMID:28594918

An assessment of predominant causal factors of pilot deviations that contribute to runway incursions

NASA Astrophysics Data System (ADS)

Campbell, Denado M.

The aim of this study was to identify predominant causal factors of pilot deviations in runway incursions over a two-year period. Runway incursion reports were obtained from NASA's Aviation Safety Reporting System (ASRS), and a qualitative method was used by classifying and coding each report to a specific causal factor(s). The causal factors that were used were substantiated by research from the Aircraft Owner's and Pilot's Association that found that these causal factors were the most common in runway incursion incidents and accidents. An additional causal factor was also utilized to determine the significance of pilot training in relation to runway incursions. From the reports examined, it was found that miscommunication and situational awareness have the greatest impact on pilots and are most often the major causes of runway incursions. This data can be used to assist airports, airlines, and the FAA to understand trends in pilot deviations, and to find solutions for specific problem areas in runway incursion incidents.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis.

PubMed

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-04-01

Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04-1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08-1·29), 1·10 (1·00-1·22), and 1·05 (0·92-1·20), respectively, per 1 SD increment in plasma urate. Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. Copyright © 2016 White et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

PubMed Central

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-01-01

Summary Background Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. Methods We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. Findings In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate. Interpretation Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. Funding UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. PMID:26781229

Causal Indicators Can Help to Interpret Factors

ERIC Educational Resources Information Center

Bentler, Peter M.

2016-01-01

The latent factor in a causal indicator model is no more than the latent factor of the factor part of the model. However, if the causal indicator variables are well-understood and help to improve the prediction of individuals' factor scores, they can help to interpret the meaning of the latent factor. Aguirre-Urreta, Rönkkö, and Marakas (2016)…

A Complex Systems Approach to Causal Discovery in Psychiatry.

PubMed

Saxe, Glenn N; Statnikov, Alexander; Fenyo, David; Ren, Jiwen; Li, Zhiguo; Prasad, Meera; Wall, Dennis; Bergman, Nora; Briggs, Ernestine C; Aliferis, Constantin

2016-01-01

Conventional research methodologies and data analytic approaches in psychiatric research are unable to reliably infer causal relations without experimental designs, or to make inferences about the functional properties of the complex systems in which psychiatric disorders are embedded. This article describes a series of studies to validate a novel hybrid computational approach--the Complex Systems-Causal Network (CS-CN) method-designed to integrate causal discovery within a complex systems framework for psychiatric research. The CS-CN method was first applied to an existing dataset on psychopathology in 163 children hospitalized with injuries (validation study). Next, it was applied to a much larger dataset of traumatized children (replication study). Finally, the CS-CN method was applied in a controlled experiment using a 'gold standard' dataset for causal discovery and compared with other methods for accurately detecting causal variables (resimulation controlled experiment). The CS-CN method successfully detected a causal network of 111 variables and 167 bivariate relations in the initial validation study. This causal network had well-defined adaptive properties and a set of variables was found that disproportionally contributed to these properties. Modeling the removal of these variables resulted in significant loss of adaptive properties. The CS-CN method was successfully applied in the replication study and performed better than traditional statistical methods, and similarly to state-of-the-art causal discovery algorithms in the causal detection experiment. The CS-CN method was validated, replicated, and yielded both novel and previously validated findings related to risk factors and potential treatments of psychiatric disorders. The novel approach yields both fine-grain (micro) and high-level (macro) insights and thus represents a promising approach for complex systems-oriented research in psychiatry.

IQ and Schizophrenia in a Swedish National Sample: Their Causal Relationship and the Interaction of IQ with Genetic Risk

PubMed Central

Kendler, Kenneth S.; Ohlsson, Henrik; Sundquist, Jan; Sundquist, Kristina

2015-01-01

Objective To clarify the relationship between IQ and subsequent risk for schizophrenia. Method IQ was assessed at ages 18-20 in 1,204,983 Swedish males born 1951-1975. Schizophrenia was assessed by hospital diagnosis through 2010. Results IQ had a monotonic relationship with schizophrenia risk across the IQ range with a mean change of 3.8% in risk per IQ point. This association, stronger in the lower versus higher IQ range, was similar if onsets within five years of testing were censored. No increased risk for schizophrenia was seen in those with highest intelligence. Co-relative control analyses showed a similar IQ-schizophrenia association in the general population and in cousin, half-sibling and full-sibling pairs. A robust interaction was seen between genetic liability to schizophrenia and IQ in predicting schizophrenia risk. Genetic susceptibility for schizophrenia had a much stronger impact on risk of illness for those with low versus high intelligence. The IQ-genetic liability interaction arose largely from IQ differences between close relatives. Conclusions IQ assessed in late adolescence is a robust risk factor for subsequent onset of schizophrenia. This association is not the result of a declining IQ associated with insidious onset. In this large, representative sample, we found no evidence for a link between genius and schizophrenia. Co-relative control analyses show that the association between lower IQ and schizophrenia is not the result of shared familial risk factors and may be causal. The strongest effect was seen with IQ differences within families. High intelligence substantially attenuates the impact of genetic liability on the risk for schizophrenia. PMID:25727538

Inhibitory Control in Siblings Discordant for Exposure to Maternal Smoking during Pregnancy

ERIC Educational Resources Information Center

Micalizzi, Lauren; Marceau, Kristine; Brick, Leslie A.; Palmer, Rohan H.; Todorov, Alexandre A.; Heath, Andrew C.; Evans, Allison; Knopik, Valerie S.

2018-01-01

Maternal smoking during pregnancy (SDP) has been linked to poorer offspring executive function across development, but SDP does not occur independent of other familial risk factors. As such, poor and inconsistent control for potential confounds, notably shared familial (i.e., genetic and environmental) confounds, preclude concluding causal effects…

Capture Hi-C identifies a novel causal gene, IL20RA, in the pan-autoimmune genetic susceptibility region 6q23.

PubMed

McGovern, Amanda; Schoenfelder, Stefan; Martin, Paul; Massey, Jonathan; Duffus, Kate; Plant, Darren; Yarwood, Annie; Pratt, Arthur G; Anderson, Amy E; Isaacs, John D; Diboll, Julie; Thalayasingam, Nishanthi; Ospelt, Caroline; Barton, Anne; Worthington, Jane; Fraser, Peter; Eyre, Stephen; Orozco, Gisela

2016-11-01

The identification of causal genes from genome-wide association studies (GWAS) is the next important step for the translation of genetic findings into biologically meaningful mechanisms of disease and potential therapeutic targets. Using novel chromatin interaction detection techniques and allele specific assays in T and B cell lines, we provide compelling evidence that redefines causal genes at the 6q23 locus, one of the most important loci that confers autoimmunity risk. Although the function of disease-associated non-coding single nucleotide polymorphisms (SNPs) at 6q23 is unknown, the association is generally assigned to TNFAIP3, the closest gene. However, the DNA fragment containing the associated SNPs interacts through chromatin looping not only with TNFAIP3, but also with IL20RA, located 680 kb upstream. The risk allele of the most likely causal SNP, rs6927172, is correlated with both a higher frequency of interactions and increased expression of IL20RA, along with a stronger binding of both the NFκB transcription factor and chromatin marks characteristic of active enhancers in T-cells. Our results highlight the importance of gene assignment for translating GWAS findings into biologically meaningful mechanisms of disease and potential therapeutic targets; indeed, monoclonal antibody therapy targeting IL-20 is effective in the treatment of rheumatoid arthritis and psoriasis, both with strong GWAS associations to this region.

Why cachexia kills: examining the causality of poor outcomes in wasting conditions.

PubMed

Kalantar-Zadeh, Kamyar; Rhee, Connie; Sim, John J; Stenvinkel, Peter; Anker, Stefan D; Kovesdy, Csaba P

2013-06-01

Weight loss is the hallmark of any progressive acute or chronic disease state. In its extreme form of significant lean body mass (including skeletal muscle) and fat loss, it is referred to as cachexia. It has been known for millennia that muscle and fat wasting leads to poor outcomes including death. On one hand, conditions and risk factors that lead to cachexia and inadequate nutrition may independently lead to increased mortality. Additionaly, cachexia per se, withdrawal of nutritional support in progressive cachexia, and advanced age may lead to death via cachexia-specific pathways. Despite the strong and consistent association of cachexia with mortality, no unifying mechanism has yet been suggested as to why wasting conditions are associated with an exceptionally high mortality risk. Hence, the causality of the cachexia-death association, even though it is biologically plausible, is widely unknown. This century-long uncertainty may have played a role as to why the field of cachexia treatment development has not shown major advances over the past decades. We suggest that cachexia-associated relative thrombocytosis and platelet activation may play a causal role in cachexia-related death, while other mechanisms may also contribute including arrhythmia-associated sudden deaths, endocrine disorders such as hypothyroidism, and immune system compromise leading to infectious events and deaths. Multidimensional research including examining biologically plausible models is urgently needed to investigate the causality of the cachexia-death association.

Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference.

PubMed

Corbin, Laura J; Tan, Vanessa Y; Hughes, David A; Wade, Kaitlin H; Paul, Dirk S; Tansey, Katherine E; Butcher, Frances; Dudbridge, Frank; Howson, Joanna M; Jallow, Momodou W; John, Catherine; Kingston, Nathalie; Lindgren, Cecilia M; O'Donavan, Michael; O'Rahilly, Stephen; Owen, Michael J; Palmer, Colin N A; Pearson, Ewan R; Scott, Robert A; van Heel, David A; Whittaker, John; Frayling, Tim; Tobin, Martin D; Wain, Louise V; Smith, George Davey; Evans, David M; Karpe, Fredrik; McCarthy, Mark I; Danesh, John; Franks, Paul W; Timpson, Nicholas J

2018-02-19

Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner.

Risk factors for neck and upper extremity disorders among computers users and the effect of interventions: an overview of systematic reviews.

PubMed

Andersen, Johan H; Fallentin, Nils; Thomsen, Jane F; Mikkelsen, Sigurd

2011-05-12

To summarize systematic reviews that 1) assessed the evidence for causal relationships between computer work and the occurrence of carpal tunnel syndrome (CTS) or upper extremity musculoskeletal disorders (UEMSDs), or 2) reported on intervention studies among computer users/or office workers. PubMed, Embase, CINAHL and Web of Science were searched for reviews published between 1999 and 2010. Additional publications were provided by content area experts. The primary author extracted all data using a purpose-built form, while two of the authors evaluated the quality of the reviews using recommended standard criteria from AMSTAR; disagreements were resolved by discussion. The quality of evidence syntheses in the included reviews was assessed qualitatively for each outcome and for the interventions. Altogether, 1,349 review titles were identified, 47 reviews were retrieved for full text relevance assessment, and 17 reviews were finally included as being relevant and of sufficient quality. The degrees of focus and rigorousness of these 17 reviews were highly variable. Three reviews on risk factors for carpal tunnel syndrome were rated moderate to high quality, 8 reviews on risk factors for UEMSDs ranged from low to moderate/high quality, and 6 reviews on intervention studies were of moderate to high quality. The quality of the evidence for computer use as a risk factor for CTS was insufficient, while the evidence for computer use and UEMSDs was moderate regarding pain complaints and limited for specific musculoskeletal disorders. From the reviews on intervention studies no strong evidence based recommendations could be given. Computer use is associated with pain complaints, but it is still not very clear if this association is causal. The evidence for specific disorders or diseases is limited. No effective interventions have yet been documented.

Enhanced circulating transforming growth factor beta 1 is causally associated with an increased risk of hepatocellular carcinoma: a mendelian randomization meta-analysis.

PubMed

Lu, Wei-Qun; Qiu, Ji-Liang; Huang, Zhi-Liang; Liu, Hai-Ying

2016-12-20

The aim of this study was to test the causal association between circulating transforming growth factor beta 1 (protein: TGF-β1 and coding gene: TGFB1) and hepatocellular carcinoma by choosing TGFB1 gene C-509T polymorphism as an instrument in a Mendelian randomization (MR) meta-analysis. Ten English articles were identified for analysis. Two authors independently assessed each article and abstracted relevant data. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were synthesized under a random-effects model. Overall, the association of C-509T polymorphism with hepatocellular carcinoma was negative, but its association with circulating TGF-β1 was statistically significant, with a higher concentration observed in carriers of the -509TT genotype (WMD, 95% CI, P: 1.72, 0.67-2.78, 0.001) and -509TT/-509TC genotypes (WMD, 95% CI, P: 0.98, 0.43-1.53, < 0.001). In subgroup analysis, C-509T polymorphism was significantly associated with hepatocellular carcinoma in population-based studies under homozygous-genotype (OR, 95% CI, P: 1.74, 1.08-2.80, 0.023) and dominant (OR, 95% CI, P: 1.48, 1.01-2.17, 0.047) models. Further MR analysis indicated that per unit increase in circulating TGF-β1 was significantly associated with a 38% (95% CI: 1.03-4.65) and 49% (95% CI: 1.01-6.06) increased risk of hepatocellular carcinoma under homozygous-genotype and dominant models, respectively. Conclusively, based on a MR meta-analysis, our findings suggest that enhanced circulating TGF-β1 is causally associated with an increased risk of hepatocellular carcinoma.

Role of Adiponectin in Coronary Heart Disease Risk

PubMed Central

Lawlor, Debbie A.; de Oliveira, Cesar; White, Jon; Horta, Bernardo Lessa; Barros, Aluísio J.D.

2016-01-01

Rationale: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis. Objective: We aimed to investigate the causal effect of adiponectin on CHD risk. Methods and Results: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68–1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84–1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors. Conclusions: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis. PMID:27252388

Cancer risk and the complexity of the interactions between environmental and host factors: HENVINET interactive diagrams as simple tools for exploring and understanding the scientific evidence.

PubMed

Merlo, Domenico F; Filiberti, Rosangela; Kobernus, Michael; Bartonova, Alena; Gamulin, Marija; Ferencic, Zeljko; Dusinska, Maria; Fucic, Aleksandra

2012-06-28

Development of graphical/visual presentations of cancer etiology caused by environmental stressors is a process that requires combining the complex biological interactions between xenobiotics in living and occupational environment with genes (gene-environment interaction) and genomic and non-genomic based disease specific mechanisms in living organisms. Traditionally, presentation of causal relationships includes the statistical association between exposure to one xenobiotic and the disease corrected for the effect of potential confounders. Within the FP6 project HENVINET, we aimed at considering together all known agents and mechanisms involved in development of selected cancer types. Selection of cancer types for causal diagrams was based on the corpus of available data and reported relative risk (RR). In constructing causal diagrams the complexity of the interactions between xenobiotics was considered a priority in the interpretation of cancer risk. Additionally, gene-environment interactions were incorporated such as polymorphisms in genes for repair and for phase I and II enzymes involved in metabolism of xenobiotics and their elimination. Information on possible age or gender susceptibility is also included. Diagrams are user friendly thanks to multistep access to information packages and the possibility of referring to related literature and a glossary of terms. Diagrams cover both chemical and physical agents (ionizing and non-ionizing radiation) and provide basic information on the strength of the association between type of exposure and cancer risk reported by human studies and supported by mechanistic studies. Causal diagrams developed within HENVINET project represent a valuable source of information for professionals working in the field of environmental health and epidemiology, and as educational material for students. Cancer risk results from a complex interaction of environmental exposures with inherited gene polymorphisms, genetic burden collected during development and non genomic capacity of response to environmental insults. In order to adopt effective preventive measures and the associated regulatory actions, a comprehensive investigation of cancer etiology is crucial. Variations and fluctuations of cancer incidence in human populations do not necessarily reflect environmental pollution policies or population distribution of polymorphisms of genes known to be associated with increased cancer risk. Tools which may be used in such a comprehensive research, including molecular biology applied to field studies, require a methodological shift from the reductionism that has been used until recently as a basic axiom in interpretation of data. The complexity of the interactions between cells, genes and the environment, i.e. the resonance of the living matter with the environment, can be synthesized by systems biology. Within the HENVINET project such philosophy was followed in order to develop interactive causal diagrams for the investigation of cancers with possible etiology in environmental exposure. Causal diagrams represent integrated knowledge and seed tool for their future development and development of similar diagrams for other environmentally related diseases such as asthma or sterility. In this paper development and application of causal diagrams for cancer are presented and discussed.

Type 2 Diabetes, Diabetes Genetic Score and Risk of Decreased Renal Function and Albuminuria: A Mendelian Randomization Study

PubMed Central

Xu, Min; Bi, Yufang; Huang, Ya; Xie, Lan; Hao, Mingli; Zhao, Zhiyun; Xu, Yu; Lu, Jieli; Chen, Yuhong; Sun, Yimin; Qi, Lu; Wang, Weiqing; Ning, Guang

2016-01-01

Background Type 2 diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, whether the association is causal remains unestablished. Research Design and Methods We performed a Mendelian Randomization (MR) analysis in 11,502 participants aged 40 and above, from a well-defined community in Shanghai during 2011–2013, to explore the causal association between T2D and decreased estimated GFR (eGFR) and increased urinary albumin-to-creatinine ratio (uACR). We genotyped 34 established T2D common variants in East Asians, and created a T2D-genetic risk score (GRS). We defined decreased eGFR as eGFR < 90 ml/min/1.73 m2 and increased uACR as uACR ≥ 30 mg/g. We used the T2D_GRS as the instrumental variable (IV) to quantify the causal effect of T2D on decreased eGFR and increased uACR. Results Each 1-standard deviation (SD, 3.90 points) increment in T2D_GRS was associated with decreased eGFR: odds ratio (OR) = 1.18 (95% confidence interval [CI]: 1.01, 1.30). In the MR analysis, we demonstrated a causal relationship between genetically determined T2D and decreased eGFR (OR = 1.47, 95% CI: 1.15, 1.88, P = 0.0003). When grouping the genetic loci according to their relations with either insulin secretion (IS) or insulin resistance (IR), we found both IS_GRS and IR_GRS were significantly related to decreased eGFR (both P < 0.02). In addition, T2D_GRS and IS_GRS were significantly associated with Log-uACR (both P = 0.04). Conclusion Our results provide novel evidence for a causal association between T2D and decreased eGFR by using MR approach in a Chinese population. PMID:27211558

Type 2 Diabetes, Diabetes Genetic Score and Risk of Decreased Renal Function and Albuminuria: A Mendelian Randomization Study.

PubMed

Xu, Min; Bi, Yufang; Huang, Ya; Xie, Lan; Hao, Mingli; Zhao, Zhiyun; Xu, Yu; Lu, Jieli; Chen, Yuhong; Sun, Yimin; Qi, Lu; Wang, Weiqing; Ning, Guang

2016-04-01

Type 2 diabetes (T2D) is a risk factor for dysregulation of glomerular filtration rate (GFR) and albuminuria. However, whether the association is causal remains unestablished. We performed a Mendelian Randomization (MR) analysis in 11,502 participants aged 40 and above, from a well-defined community in Shanghai during 2011-2013, to explore the causal association between T2D and decreased estimated GFR (eGFR) and increased urinary albumin-to-creatinine ratio (uACR). We genotyped 34 established T2D common variants in East Asians, and created a T2D-genetic risk score (GRS). We defined decreased eGFR as eGFR<90ml/min/1.73m(2) and increased uACR as uACR≥30mg/g. We used the T2D_GRS as the instrumental variable (IV) to quantify the causal effect of T2D on decreased eGFR and increased uACR. Each 1-standard deviation (SD, 3.90 points) increment in T2D_GRS was associated with decreased eGFR: odds ratio (OR)=1.18 (95% confidence interval [CI]: 1.01, 1.30). In the MR analysis, we demonstrated a causal relationship between genetically determined T2D and decreased eGFR (OR=1.47, 95% CI: 1.15, 1.88, P=0.0003). When grouping the genetic loci according to their relations with either insulin secretion (IS) or insulin resistance (IR), we found both IS_GRS and IR_GRS were significantly related to decreased eGFR (both P<0.02). In addition, T2D_GRS and IS_GRS were significantly associated with Log-uACR (both P=0.04). Our results provide novel evidence for a causal association between T2D and decreased eGFR by using MR approach in a Chinese population. Copyright © 2016. Published by Elsevier B.V.

A narrative review of alcohol consumption as a risk factor for global burden of disease.

PubMed

Rehm, Jürgen; Imtiaz, Sameer

2016-10-28

Since the original Comparative Risk Assessment (CRA) for alcohol consumption as part of the Global Burden of Disease Study for 1990, there had been regular updates of CRAs for alcohol from the World Health Organization and/or the Institute for Health Metrics and Evaluation. These studies have become more and more refined with respect to establishing causality between dimensions of alcohol consumption and different disease and mortality (cause of death) outcomes, refining risk relations, and improving the methodology for estimating exposure and alcohol-attributable burden. The present review will give an overview on the main results of the CRAs with respect to alcohol consumption as a risk factor, sketch out new trends and developments, and draw implications for future research and policy.

Risk factors for breast cancer by oestrogen receptor status: a population-based case-control study.

PubMed Central

Cooper, J. A.; Rohan, T. E.; Cant, E. L.; Horsfall, D. J.; Tilley, W. D.

1989-01-01

Data from a population-based case-control study conducted in Adelaide, South Australia, and involving 451 case-control pairs, were analysed to determine whether the associations of menstrual, reproductive, dietary and other factors with risk of breast cancer differed by oestrogen receptor (ER) status. Data on ER status were available for 380 cases. The proportion of tumours which were ER+ increased with age, and there was a higher proportion of ER+ tumours in post-menopausal than in premenopausal women. Both oral contraceptive use (P = 0.055) and cigarette smoking (P = 0.047) were associated with increased (unadjusted) risk of ER- cancer, while having little association with risk of ER+ cancer. Most dietary factors had little association with risk of either cancer type, the main exception being the reduction in risk of ER- breast cancer with increasing beta-carotene intake (P for trend = 0.017). In general, however, links with the factors examined were not strong enough to suggest different causal pathways for ER- and ER+ breast cancer. PMID:2757918

Panic disorder and cardiovascular diseases: an overview.

PubMed

Machado, Sergio; Sancassiani, Federica; Paes, Flavia; Rocha, Nuno; Murillo-Rodriguez, Eric; Nardi, Antonio Egidio

2017-10-01

The association between panic disorder (PD) and cardiovascular diseases (CVD) has been extensively studied in recent years and, although some studies have shown anxiety disorders co-existing or increasing the risk of heart disease, no causal hypothesis has been well established. Thus, a critical review was performed of the studies that evaluated the association between PD and cardiovascular diseases; synthesizing the evidence on the mechanisms mediators that theoretically would be the responsible for the causal pathway between PD and CVD, specifically. This overview shows epidemiological studies, and discusses biological mechanisms that could link PD to CVD, such as pleiotropy, heart rate variability, unhealthy lifestyle, atherosclerosis, mental stress, and myocardial perfusion defects. This study tried to provide a comprehensive narrative synthesis of previously published information regarding PD and CVD and open new possibilities of clinical management and pathophysiological understanding. Some epidemiological studies have indicated that PD could be a risk factor for CVD, raising morbidity and mortality in PD, suggesting an association between them. These studies argue that PD pathophysiology could cause or potentiate CVD. However, there is no evidence in favour of a causal relationship between PD and CVD. Therefore, PD patients with suspicions of cardiovascular symptoms need redoubled attention.

Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome

PubMed Central

Day, Felix R.; Hinds, David A.; Tung, Joyce Y.; Stolk, Lisette; Styrkarsdottir, Unnur; Saxena, Richa; Bjonnes, Andrew; Broer, Linda; Dunger, David B.; Halldorsson, Bjarni V.; Lawlor, Debbie A.; Laval, Guillaume; Mathieson, Iain; McCardle, Wendy L.; Louwers, Yvonne; Meun, Cindy; Ring, Susan; Scott, Robert A.; Sulem, Patrick; Uitterlinden, André G.; Wareham, Nicholas J.; Thorsteinsdottir, Unnur; Welt, Corrine; Stefansson, Kari; Laven, Joop S. E.; Ong, Ken K.; Perry, John R. B.

2015-01-01

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further ∼2,000 clinically validated cases and ∼100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 × 10−8), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P=2.5 × 10−9), higher insulin resistance (P=6 × 10−4) and lower serum sex hormone binding globulin concentrations (P=5 × 10−4). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P=1.6 × 10−8) and PCOS-susceptibility alleles are associated with higher serum anti-Müllerian hormone concentrations in girls (P=8.9 × 10−5). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk. PMID:26416764

Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome.

PubMed

Day, Felix R; Hinds, David A; Tung, Joyce Y; Stolk, Lisette; Styrkarsdottir, Unnur; Saxena, Richa; Bjonnes, Andrew; Broer, Linda; Dunger, David B; Halldorsson, Bjarni V; Lawlor, Debbie A; Laval, Guillaume; Mathieson, Iain; McCardle, Wendy L; Louwers, Yvonne; Meun, Cindy; Ring, Susan; Scott, Robert A; Sulem, Patrick; Uitterlinden, André G; Wareham, Nicholas J; Thorsteinsdottir, Unnur; Welt, Corrine; Stefansson, Kari; Laven, Joop S E; Ong, Ken K; Perry, John R B

2015-09-29

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further ∼2,000 clinically validated cases and ∼100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 × 10(-8)), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P=2.5 × 10(-9)), higher insulin resistance (P=6 × 10(-4)) and lower serum sex hormone binding globulin concentrations (P=5 × 10(-4)). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P=1.6 × 10(-8)) and PCOS-susceptibility alleles are associated with higher serum anti-Müllerian hormone concentrations in girls (P=8.9 × 10(-5)). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk.

A Bayesian network approach for causal inferences in pesticide risk assessment and management

EPA Science Inventory

Pesticide risk assessment and management must balance societal benefits and ecosystem protection, based on quantified risks and the strength of the causal linkages between uses of the pesticide and socioeconomic and ecological endpoints of concern. A Bayesian network (BN) is a gr...

Toxic-Metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management and Future Research

PubMed Central

Husain, Sohail Z.; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D.; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y.; Schwarzenberg, Sarah Jane; Usatin, Danielle; Uc, Aliye

2016-01-01

Objectives Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies and their rationale. Methods We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: (a) hyperlipidemia, (b) hypercalcemia, (c) chronic renal failure, (d) smoking exposure, (e) alcohol, and (f) medications. Areas of additional research were identified. Results Hypertriglyceridemia of 1000 mg/dl or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and by-stander status may be implicated. Other pancreatitis risk factors must be sought in all cases. Conclusions The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/ removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children. PMID:26594832

Toxic-metabolic Risk Factors in Pediatric Pancreatitis: Recommendations for Diagnosis, Management, and Future Research.

PubMed

Husain, Sohail Z; Morinville, Veronique; Pohl, John; Abu-El-Haija, Maisam; Bellin, Melena D; Freedman, Steve; Hegyi, Peter; Heyman, Melvin B; Himes, Ryan; Ooi, Chee Y; Schwarzenberg, Sarah J; Usatin, Danielle; Uc, Aliye

2016-04-01

Pancreatitis in children can result from metabolic and toxic risk factors, but the evidence linking these factors is sparse. We review the evidence for association or causality of these risk factors in pancreatitis, discuss management strategies, and their rationale. We conducted a review of the pediatric pancreatitis literature with respect to the following risk factors: hyperlipidemia, hypercalcemia, chronic renal failure, smoking exposure, alcohol, and medications. Areas of additional research were identified. Hypertriglyceridemia of 1000 mg/dL or greater poses an absolute risk for pancreatitis; persistent elevations of calcium are predisposing. Further research is necessary to determine whether end-stage renal disease leads to increased pancreatitis in children similar to adults. It is unknown whether cigarette smoking exposure, which clearly increases risk in adults, also increases risk in children. The role of alcohol in pediatric pancreatitis, whether direct or modifying, needs to be elucidated. The evidence supporting most cases of medication-induced pancreatitis is poor. Drug structure, improper handling of drug by host, and bystander status may be implicated. Other pancreatitis risk factors must be sought in all cases. The quality of evidence supporting causative role of various toxic and metabolic factors in pediatric pancreatitis is variable. Careful phenotyping is essential, including search for other etiologic risk factors. Directed therapy includes correction/removal of any agent identified, and general supportive measures. Further research is necessary to improve our understanding of these pancreatitis risk factors in children.

Drug- and Herb-Induced Liver Injury in Clinical and Translational Hepatology: Causality Assessment Methods, Quo Vadis?

PubMed Central

Eickhoff, Axel; Schulze, Johannes

2013-01-01

Drug-induced liver injury (DILI) and herb-induced liver injury (HILI) are typical diseases of clinical and translational hepatology. Their diagnosis is complex and requires an experienced clinician to translate basic science into clinical judgment and identify a valid causality algorithm. To prospectively assess causality starting on the day DILI or HILI is suspected, the best approach for physicians is to use the Council for International Organizations of Medical Sciences (CIOMS) scale in its original or preferably its updated version. The CIOMS scale is validated, liver-specific, structured, and quantitative, providing final causality grades based on scores of specific items for individual patients. These items include latency period, decline in liver values after treatment cessation, risk factors, co-medication, alternative diagnoses, hepatotoxicity track record of the suspected product, and unintentional re-exposure. Provided causality is established as probable or highly probable, data of the CIOMS scale with all individual items, a short clinical report, and complete raw data should be transmitted to the regulatory agencies, manufacturers, expert panels, and possibly to the scientific community for further refinement of the causality evaluation in a setting of retrospective expert opinion. Good-quality case data combined with thorough CIOMS-based assessment as a standardized approach should avert subsequent necessity for other complex causality assessment methods that may have inter-rater problems because of poor-quality data. In the future, the CIOMS scale will continue to be the preferred tool to assess causality of DILI and HILI cases and should be used consistently, both prospectively by physicians, and retrospectively for subsequent expert opinion if needed. For comparability and international harmonization, all parties assessing causality in DILI and HILI cases should attempt this standardized approach using the updated CIOMS scale. PMID:26357608

A Prospective Examination of Perceived Burdensomeness and Thwarted Belongingness As Risk Factors for Suicide Ideation In Adult Outpatients Receiving Cognitive-Behavioral Therapy.

PubMed

Teismann, Tobias; Glaesmer, Heide; von Brachel, Ruth; Siegmann, Paula; Forkmann, Thomas

2017-10-01

The interpersonal-psychological theory of suicidal behavior posits that 2 proximal, causal, and interactive risk factors must be present for someone to desire suicide: perceived burdensomeness and thwarted belongingness. The purpose of the present study was to evaluate the predictive power of these 2 risk factors in a prospective study. A total of 231 adult outpatients (age: mean = 38.1, standard deviation = 12.3) undergoing cognitive-behavioral therapy took part in a pretreatment and a midtreatment assessment after the 10th therapy session. Perceived burdensomeness, thwarted belongingness, and the interaction between these 2 risk factors did not add incremental variance to the prediction of midtreatment suicide ideation after controlling for age, gender, depression, hopelessness, impulsivity, lifetime suicide attempts, and pretreatment suicide ideation. The best predictor of midtreatment suicide ideation was pretreatment suicide ideation. Results offer only limited support to the assumptions of the interpersonal theory of suicide. © 2017 Wiley Periodicals, Inc.

Paraphilic Sexual Interests and Sexually Coercive Behavior: A Population-Based Twin Study.

PubMed

Baur, Elena; Forsman, Mats; Santtila, Pekka; Johansson, Ada; Sandnabba, Kenneth; Långström, Niklas

2016-07-01

Prior research with selected clinical and forensic samples suggests associations between paraphilic sexual interests (e.g., exhibitionism and sexual sadism) and sexually coercive behavior. However, no study to date used a large, representative and genetically informative population sample to address the potential causal nature of this association. We used self-report data on paraphilic and sexually coercive behavior from 5990 18- to 32-year-old male and female twins from a contemporary Finnish population cohort. Logistic regression and co-twin control models were employed to examine if paraphilic behaviors were causally related to coercive behavior or if suggested links were confounded by familial (genetic or common family environment) risk factors. Results indicated that associations between four out of five tested paraphilic behaviors (exhibitionism, masochism, sadism, and voyeurism, respectively) and sexually coercive behavior were moderate to strong. Transvestic fetishism was not independently associated with sexual coercion. Comparisons of twins reporting paraphilic behavior with their paraphilic behavior-discordant twin further suggested that associations were largely independent of shared genetic and environmental confounds, consistent with a causal association. In conclusion, similar to previously reported predictive effects of paraphilias on sexual crime recidivism, paraphilic behavior among young adults in the general population increases sexual offending risk. Further, early identification of paraphilic interest and preventive interventions with at-risk individuals might also reduce perpetration of first-time sexual violence.

Social relationships and risk of dementia: a population-based study.

PubMed

Sörman, Daniel Eriksson; Rönnlund, Michael; Sundström, Anna; Adolfsson, Rolf; Nilsson, Lars-Göran

2015-08-01

The objective was to examine whether aspects of social relationships in old age are associated with all-cause dementia and Alzheimer's disease (AD). We studied 1,715 older adults (≥ 65 years) who were dementia-free at baseline over a period of up to 16 years. Data on living status, contact/visit frequency, satisfaction with contact frequency, and having/not having a close friend were analyzed using Cox proportional hazards regressions with all-cause dementia or AD as the dependent variable. To control for reverse causality and to identify potential long-term effects, we additionally performed analyses with delayed entry. We identified 373 incident cases of dementia (207 with AD) during follow-up. The variable visiting/visits from friends was associated with reduced risk of all-cause dementia. Further, a higher value on the relationships index (sum of all variables) was associated with reduced risk of all-cause dementia and AD. However, in analyses with delayed entry, restricted to participants with a survival time of three years or more, none of the social relationship variables was associated with all-cause dementia or AD. The results indicate that certain aspects of social relationships are associated with incident dementia or AD, but also that these associations may reflect reverse causality. Future studies aimed at identifying other factors of a person's social life that may have the potential to postpone dementia should consider the effects of reverse causality.

Tobacco carcinogen (NNK) induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation

USDA-ARS?s Scientific Manuscript database

Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carc...

Educational Mismatch and Spatial Flexibility in Italian Local Labour Markets

ERIC Educational Resources Information Center

Croce, Giuseppe; Ghignoni, Emanuela

2015-01-01

According to recent literature, this paper highlights the relevance of spatial mobility as an explanatory factor of the individual risk of job-education mismatch. To investigate this causal link, we use individual information about daily home-to-work commuting time and choices to relocate in a different local area to get a job. Our model takes…

Perceived risk of cervical cancer among pre-screening age women (18-24 years): the impact of information about cervical cancer risk factors and the causal role of HPV.

PubMed

Nadarzynski, Tomasz; Waller, Jo; Robb, Kathryn A; Marlow, Laura A V

2012-10-01

Current National Health Service cervical screening information does not explain that the cause of cervical cancer is a sexually transmitted infection (human papillomavirus (HPV)). This study aimed to consider the impact that providing this information, in addition to risk factor information, might have on women's perceived risk of cervical cancer. Female students aged 18-24 years (n=606) completed a web-based survey and were randomised to receive (1) control information about cervical cancer; (2) details of the link between HPV and cervical cancer; (3) risk factor information or (4) details about the link with HPV + risk factor information. Risk perceptions for cervical cancer were assessed before and after reading the information. There was a significant difference in perceived risk of cervical cancer between the four groups following information exposure (p=0.002). Compared with the control group, risk perceptions were significantly lower among women given risk factor information but not among those informed about HPV. There were significant group by risk factor interactions for smoking status (p<0.001), age of first sex (p=0.018) and number of sexual partners (p<0.001). Risk perceptions were lower among women considered at low risk and given risk factor information, but there was no association between information group and perceived risk for high-risk women. Providing risk factor information appears to reduce cervical cancer risk perceptions, but learning about the aetiological role of HPV appears to have no impact on risk perceptions. Incorporating brief information about HPV as the cause of cervical cancer should be in addition to, rather than in place of, risk factor information.

To what extent can theory account for the findings of road safety evaluation studies?

PubMed

Elvik, Rune

2004-09-01

This paper proposes a conceptual framework that can be used to assess to what extent the findings of road safety evaluation research make sense from a theoretical point of view. The effects of road safety measures are modelled as passing through two causal chains. One of these, termed the engineering effect, refers to the intended effects of a road safety measure on a set of risk factors related to accident occurrence or injury severity. The engineering effect of road safety measures is modelled in terms of nine basic risk factors, one or more of which any road safety measure needs to influence in order to have the intended effect on accidents or injuries. The other causal chain producing the effects of road safety measures is termed the behavioural effect, and refers to road user behavioural adaptations to road safety measures. The behavioural effect is related to the engineering effect, in the sense that certain properties of the engineering effect of a road safety measure influence the likelihood that behavioural adaptation will occur. The behavioural effect of a road safety measure is modelled in terms of six factors that influence the likelihood that behavioural adaptation will occur. The nine basic risk factors representing the engineering effect of a road safety measure, and the six factors influencing the likelihood of behavioural adaptation can be used as checklists in assessing whether or not the findings of road safety evaluation studies make sense from a theoretical point of view. At the current state of knowledge, a more stringent evaluation of the extent to which theory can explain the findings of road safety evaluation studies is, in most cases, not possible. Copyright 2003 Elsevier Ltd.

The Moderating Effect of Mental Toughness: Perception of Risk and Belief in the Paranormal.

PubMed

Drinkwater, Kenneth; Dagnall, Neil; Denovan, Andrew; Parker, Andrew

2018-01-01

This research demonstrates that higher levels of mental toughness provide cognitive-perceptual processing advantages when evaluating risk. No previous research, however, has examined mental toughness in relation to perception of risk and paranormal belief (a variable associated with distorted perception of causality and elevated levels of perceived risk). Accordingly, the present paper investigated relationships between these factors. A sample of 174 participants completed self-report measures assessing mental toughness, general perception of risk, and paranormal belief. Responses were analyzed via correlations and moderation analyses. Results revealed that mental toughness correlated negatively with perception of risk and paranormal belief, whereas paranormal belief correlated positively with perception of risk. For the moderation effects, simple slopes analyses indicated that high levels of MT and subfactors of commitment and confidence reduced the strength of association between paranormal belief and perceived risk. Therefore, MT potentially acts as a protective factor among individuals who believe in the paranormal, reducing the tendency to perceive elevated levels of risk.

Environmental conditions and Puumala virus transmission in Belgium

PubMed Central

Linard, Catherine; Tersago, Katrien; Leirs, Herwig; Lambin, Eric F

2007-01-01

Background Non-vector-borne zoonoses such as Puumala hantavirus (PUUV) can be transmitted directly, by physical contact between infected and susceptible hosts, or indirectly, with the environment as an intermediate. The objective of this study is to better understand the causal link between environmental features and PUUV prevalence in bank vole population in Belgium, and hence with transmission risk to humans. Our hypothesis was that environmental conditions controlling the direct and indirect transmission paths differ, such that the risk of transmission to humans is not only determined by host abundance. We explored the relationship between, on one hand, environmental variables and, on the other hand, host abundance, PUUV prevalence in the host, and human cases of nephropathia epidemica (NE). Statistical analyses were carried out on 17 field sites situated in Belgian broadleaf forests. Results Linear regressions showed that landscape attributes, particularly landscape configuration, influence the abundance of hosts in broadleaf forests. Based on logistic regressions, we show that PUUV prevalence among bank voles is more linked to variables favouring the survival of the virus in the environment, and thus the indirect transmission: low winter temperatures are strongly linked to prevalence among bank voles, and high soil moisture is linked to the number of NE cases among humans. The transmission risk to humans therefore depends on the efficiency of the indirect transmission path. Human risk behaviours, such as the propensity for people to go in forest areas that best support the virus, also influence the number of human cases. Conclusion The transmission risk to humans of non-vector-borne zoonoses such as PUUV depends on a combination of various environmental factors. To understand the complex causal pathways between the environment and disease risk, one should distinguish between environmental factors related to the abundance of hosts such as land-surface attributes, landscape configuration, and climate – i.e., host ecology, – and environmental factors related to PUUV prevalence, mainly winter temperatures and soil moisture – i.e., virus ecology. Beyond a threshold abundance of hosts, environmental factors favouring the indirect transmission path (soil and climate) can better predict the number of NE cases among humans than factors influencing the abundance of hosts. PMID:18078526

Suicidal ideation, risk factors, and communication with parents. An HBSC study on school children in Estonia, Lithuania, and Luxembourg.

PubMed

Mark, Lauraliisa; Samm, Algi; Tooding, Liina-Mai; Sisask, Merike; Aasvee, Katrin; Zaborskis, Apolinaras; Zemaitiene, Nida; Värnik, Airi

2013-01-01

Suicide is a leading cause of death among youth. In the year 2002, Lithuania had the 2nd, Luxembourg the 5th, and Estonia the 9th highest suicide rates among 15- to 19-year-olds across 90 countries worldwide. Suicidal ideation is a significant precursor to suicide. To report on the prevalence of and associations between suicidal ideation, smoking, alcohol consumption, physical fighting, bullying, and communication with parents among 15-year-old schoolchildren. The survey analyzes data from the 2005/2006 HBSC study from Estonia, Lithuania, and Luxembourg (N = 4,954). The risk factors were calculated through multinomial logistic regression analyses. The overall prevalence of suicidal ideation in the preceding year was 17%. Suicidal thoughts were associated with communication difficulties with parents (OR from 2.0 to 4.6) and other risk factors, especially multiple risks (OR for 4-5 concurrent risk factors from 4.5 to 13.6). Parent-child communication had a significant mediating effect by decreasing the odds for suicidality and multiple risks. The prevalence estimates were obtained by self-reports. The causal relationships need further investigation. The risk factors studied, particularly multiple risks, were associated with higher odds for suicidal ideation. Good parent-child communication is a significant resource for decreasing suicidal ideation among adolescents.

Climate Change and Collective Violence.

PubMed

Levy, Barry S; Sidel, Victor W; Patz, Jonathan A

2017-03-20

Climate change is causing increases in temperature, changes in precipitation and extreme weather events, sea-level rise, and other environmental impacts. It is also causing or contributing to heat-related disorders, respiratory and allergic disorders, infectious diseases, malnutrition due to food insecurity, and mental health disorders. In addition, increasing evidence indicates that climate change is causally associated with collective violence, generally in combination with other causal factors. Increased temperatures and extremes of precipitation with their associated consequences, including resultant scarcity of cropland and other key environmental resources, are major pathways by which climate change leads to collective violence. Public health professionals can help prevent collective violence due to climate change (a) by supporting mitigation measures to reduce greenhouse gas emissions, (b) by promoting adaptation measures to address the consequences of climate change and to improve community resilience, and (c) by addressing underlying risk factors for collective violence, such as poverty and socioeconomic disparities.

Epidemiología genética sobre las teorías causales y la patogénesis de la diabetes mellitus tipo 2.

PubMed

Castro-Juárez, Carlos Jonnathan; Ramírez-García, Sergio Alberto; Villa-Ruano, Nemesio; García-Cruz, Diana

2017-01-01

Diabetes mellitus type 2 (DM2) is a worldwide public health problem. The etiology of the disease is multifactorial and is characterized by great heterogeneity of metabolic disorders. The most common are the insufficient production of insulin, insulin resistance and impaired incretin system. The specialist must understand the multi-causal nature of DM2 in the post-genomic era. This nature is determined by the additive effect of genes and environment, so there is no simple genetic epidemiological model to explain the inheritance pattern. Hence the need to establish the proportion of disease that is determined by genes and the contribution of environmental factors, the combination of which regulates the threshold or tolerance level for diabetes development. Given this complexity in DM2 in this work are discussed the various existing theories of causality of this disease, which will permit us to understand the interaction between the environment and the human genome, and also to know how risk factors or predisposition to this disease influence, laying the grounds that delimit environment interaction with the genome. Copyright: © 2017 SecretarÍa de Salud.

DYNAMO-HIA–A Dynamic Modeling Tool for Generic Health Impact Assessments

PubMed Central

Lhachimi, Stefan K.; Nusselder, Wilma J.; Smit, Henriette A.; van Baal, Pieter; Baili, Paolo; Bennett, Kathleen; Fernández, Esteve; Kulik, Margarete C.; Lobstein, Tim; Pomerleau, Joceline; Mackenbach, Johan P.; Boshuizen, Hendriek C.

2012-01-01

Background Currently, no standard tool is publicly available that allows researchers or policy-makers to quantify the impact of policies using epidemiological evidence within the causal framework of Health Impact Assessment (HIA). A standard tool should comply with three technical criteria (real-life population, dynamic projection, explicit risk-factor states) and three usability criteria (modest data requirements, rich model output, generally accessible) to be useful in the applied setting of HIA. With DYNAMO-HIA (Dynamic Modeling for Health Impact Assessment), we introduce such a generic software tool specifically designed to facilitate quantification in the assessment of the health impacts of policies. Methods and Results DYNAMO-HIA quantifies the impact of user-specified risk-factor changes on multiple diseases and in turn on overall population health, comparing one reference scenario with one or more intervention scenarios. The Markov-based modeling approach allows for explicit risk-factor states and simulation of a real-life population. A built-in parameter estimation module ensures that only standard population-level epidemiological evidence is required, i.e. data on incidence, prevalence, relative risks, and mortality. DYNAMO-HIA provides a rich output of summary measures – e.g. life expectancy and disease-free life expectancy – and detailed data – e.g. prevalences and mortality/survival rates – by age, sex, and risk-factor status over time. DYNAMO-HIA is controlled via a graphical user interface and is publicly available from the internet, ensuring general accessibility. We illustrate the use of DYNAMO-HIA with two example applications: a policy causing an overall increase in alcohol consumption and quantifying the disease-burden of smoking. Conclusion By combining modest data needs with general accessibility and user friendliness within the causal framework of HIA, DYNAMO-HIA is a potential standard tool for health impact assessment based on epidemiologic evidence. PMID:22590491

Bullied at school, bullied at work: a prospective study.

PubMed

Andersen, Lars Peter; Labriola, Merete; Andersen, Johan Hviid; Lund, Thomas; Hansen, Claus D

2015-10-12

The consequences of childhood bullying victimisation are serious. Much previous research on risk factors for being bullied has used a cross-sectional design, impeding the possibility to draw conclusions on causality, and has not considered simultaneous effects of multiple risk factors. Paying closer attention to multiple risk factors for being bullying can provide a basis for designing intervention programmes to prevent or reduce bullying among children and adolescents. Risk factors for bullying were examined by using questionnaire data collected in 2004 and 2007. In 2004, the participants were aged 14-15 years and 17-18 years in 2007. The baseline questionnaire was answered by 3054 individuals in 2004, and 2181 individuals participated in both rounds. We analysed risk factors for being bullied at the individual and societal level. Information on the social background of the participants was derived from a national register at Statistics Denmark. Several risk factors were identified. Being obese, low self-assessed position in school class, overprotective parents, low self-esteem, low sense of coherence and low socioeconomic status were risk factors for being bullied at school. Being overweight, smoking, low self-assessed position in class, low sense of coherence and low socioeconomic status were risk factors for being bullied at work. However, most associations between risk factors in 2004 and being bullied in 2007 disappeared after adjustment for being bullied in 2004. The strongest risk factor for being bullied was being previously bullied. Our results stress the importance of early prevention of bullying at schools. In addition, attention should be drawn to the role of overprotective parents.

Revisiting causal neighborhood effects on individual ischemic heart disease risk: a quasi-experimental multilevel analysis among Swedish siblings.

PubMed

Merlo, Juan; Ohlsson, Henrik; Chaix, Basile; Lichtenstein, Paul; Kawachi, Ichiro; Subramanian, S V

2013-01-01

Neighborhood socioeconomic disadvantage is associated to increased individual risk of ischemic heart disease (IHD). However, the value of this association for causal inference is uncertain. Moreover, neighborhoods are often defined by available administrative boundaries without evaluating in which degree these boundaries embrace a relevant socio-geographical context that condition individual differences in IHD risk. Therefore, we performed an analysis of variance, and also compared the associations obtained by conventional multilevel analyses and by quasi-experimental family-based design that provides stronger evidence for causal inference. Linking the Swedish Multi-Generation Register to several other national registers, we analyzed 184,931 families embracing 415,540 full brothers 45-64 years old in 2004, and residing in 8408 small-area market statistics (SAMS) considered as "neighborhoods" in our study. We investigated the association between low neighborhood income (categorized in groups by deciles) and IHD risk in the next four years. We distinguished between family mean and intrafamilial-centered low neighborhood income, which allowed us to investigate both unrelated individuals from different families and full brothers within families. We applied multilevel logistic regression techniques to obtain odds ratios (OR), variance partition coefficients (VPC) and 95% credible intervals (CI). In unrelated individuals a decile unit increase of low neighborhood income increased individual IHD risk (OR = 1.04, 95% CI: 1.03-1.07). In the intrafamilial analysis this association was reduced (OR = 1.02, 95% CI: 1.02-1.04). Low neighborhood income seems associated with IHD risk in middle-aged men. However, despite the family-based design, we cannot exclude residual confounding by genetic and non-shared environmental factors. Besides, the low neighborhood level VPC = 1.5% suggest that the SAMS are a rather inappropriate construct of the socio-geographic context that conditions individual variance in IHD risk. In contrast the high family level VPC = 20.1% confirms the relevance of the family context for understanding IHD risk. Copyright © 2012 Elsevier Ltd. All rights reserved.

A methodology to model causal relationships on offshore safety assessment focusing on human and organizational factors.

PubMed

Ren, J; Jenkinson, I; Wang, J; Xu, D L; Yang, J B

2008-01-01

Focusing on people and organizations, this paper aims to contribute to offshore safety assessment by proposing a methodology to model causal relationships. The methodology is proposed in a general sense that it will be capable of accommodating modeling of multiple risk factors considered in offshore operations and will have the ability to deal with different types of data that may come from different resources. Reason's "Swiss cheese" model is used to form a generic offshore safety assessment framework, and Bayesian Network (BN) is tailored to fit into the framework to construct a causal relationship model. The proposed framework uses a five-level-structure model to address latent failures within the causal sequence of events. The five levels include Root causes level, Trigger events level, Incidents level, Accidents level, and Consequences level. To analyze and model a specified offshore installation safety, a BN model was established following the guideline of the proposed five-level framework. A range of events was specified, and the related prior and conditional probabilities regarding the BN model were assigned based on the inherent characteristics of each event. This paper shows that Reason's "Swiss cheese" model and BN can be jointly used in offshore safety assessment. On the one hand, the five-level conceptual model is enhanced by BNs that are capable of providing graphical demonstration of inter-relationships as well as calculating numerical values of occurrence likelihood for each failure event. Bayesian inference mechanism also makes it possible to monitor how a safety situation changes when information flow travel forwards and backwards within the networks. On the other hand, BN modeling relies heavily on experts' personal experiences and is therefore highly domain specific. "Swiss cheese" model is such a theoretic framework that it is based on solid behavioral theory and therefore can be used to provide industry with a roadmap for BN modeling and implications. A case study of the collision risk between a Floating Production, Storage and Offloading (FPSO) unit and authorized vessels caused by human and organizational factors (HOFs) during operations is used to illustrate an industrial application of the proposed methodology.

Genetic and non-iodine-related factors in the aetiology of nodular goitre.

PubMed

Knudsen, Nils; Brix, Thomas Heiberg

2014-08-01

Genetic and a large number of environmental non-iodine-related factors play a role in the cause of nodular goitre. Most evidence for the influence of genetic and environmental factors in the cause of goitre is from cross-sectional, population-based studies. Only a few studies have included prospective data on risk factors for nodular goitre, although few prospective data are available on the effect of iodine and tobacco smoking on goitre development. Goitre is not one single phenotype. Many epidemiological studies do not distinguish diffuse from nodular goitre, as the investigated parameter is often thyroid volume or frequency with increased thyroid volume. Moreover, information on the presence and effect of gene-environment, gene-gene, and environment-environment effect modifications is limited. Thus, firm conclusions about the relative contributions and causality of the investigated risk factors should be made with caution. Smoking seems to be an established risk factor for nodular goitre, possibly with effect modification from iodine intake, as the risk associated with smoking is smaller or absent in areas with sufficient iodine intake. The use of oral contraceptives might have protective effects against goitre, and childbirth is an increased risk factor for goitre in areas with non-optimal iodine intake. Insulin resistance is a recently investigated risk factor, and the risk of goitre may be reversible with metformin treatment. Iodine remains the major environmental risk factor for nodular goitre. Copyright © 2014 Elsevier Ltd. All rights reserved.

Overcommitment as a predictor of effort-reward imbalance: evidence from an 8-year follow-up study.

PubMed

Feldt, Taru; Hyvönen, Katriina; Mäkikangas, Anne; Rantanen, Johanna; Huhtala, Mari; Kinnunen, Ulla

2016-07-01

The effort-reward imbalance (ERI) model includes the personal characteristic of overcommitment (OC) and the job-related characteristics of effort, reward, and ERI, all of which are assumed to play a role in an employee's health and well-being at work. The aim of the present longitudinal study was to shed more light on the dynamics of the ERI model by investigating the basic hypotheses related to the role of OC in the model, ie, to establish whether an employee's OC could be a risk factor for an increased experience of high effort, low reward, and high ERI at work. The study was based on 5-wave, 8-year follow-up data collected among Finnish professionals in 2006 (T1, N=747), 2008 (T2, N=422), 2010 (T3, N=368), 2012 (T4, N=325), and 2014 (T5, N=273). The participants were mostly male (85% at T1) and the majority of them worked in technical fields. OC, effort, reward, and ERI were measured at each time point with the 23-item ERI scale. Three cross-lagged structural equation models (SEM) were estimated and compared by using full information maximum likelihood method: (i) OC predicted later experiences of effort, reward, and ERI (normal causation model), (ii) effort, reward, and ERI predicted later OC (reversed causation model), and (iii) associations in normal causal and reversed causal models were simultaneously valid (reciprocal causation model). The results supported the normal causation model: strong OC predicted later experiences of high effort, low reward and high ERI. High OC is a risk factor for an increased experience of job strain factors; that is, high effort, low reward, and high ERI. Thus, OC is a risk factor not only for an employee's well-being and health but also for an increasing risk for perceiving adverse job strain factors in the working environment.

The causal nature of the association between neighborhood deprivation and drug abuse: a prospective national Swedish co-relative control study

PubMed Central

Kendler, K. S.; Ohlsson, H.; Sundquist, K.; Sundquist, J.

2014-01-01

Background Risk for drug abuse (DA) is strongly associated with neighborhood social deprivation (SD). However, the causal nature of this relationship is unclear. Method Three Swedish population-based cohorts were followed up over 5 years for incident registration of DA in medical, legal or pharmacy records. In each cohort, we examined the SD–DA association, controlling carefully for individual socio-economic status (SES) with multiple measures, in the entire sample and among pairs of first cousins, paternal and maternal half-siblings, full siblings and monozygotic (MZ) twins discordant for SD exposure. The number of informative relative pairs ranged from 6366 to 166208. Results In all cohorts, SD was prospectively related to risk for incident DA. In relative pairs discordant for SD exposure, the SD–DA association was similar to that seen in the entire population in cousins, half-siblings, full siblings and MZ twins. Eliminating subjects who were residentially unstable or had DA in the first two follow-up years did not alter this pattern. When divided by age, in the youngest groups, the SD–DA association was weaker in siblings than in the entire population. Conclusions Across three cohorts, controlling for individual SES and confounding familial factors, SD prospectively predicted risk for incident DA registration. These results support the hypothesis that the SD–DA association is in part causal and unlikely to result entirely from personal attributes, which both increase risk for DA and cause selection into high SD environments. At least part of the SD–DA association arises because exposure to SD causes an increased risk of DA. PMID:25055172

The association between caffeine and cognitive decline: examining alternative causal hypotheses.

PubMed

Ritchie, K; Ancelin, M L; Amieva, H; Rouaud, O; Carrière, I

2014-04-01

Numerous studies suggest that higher coffee consumption may reduce the rate of aging-related cognitive decline in women. It is thus potentially a cheap and widely available candidate for prevention programs provided its mechanism may be adequately understood. The assumed effect is that of reduced amyloid deposition, however, alternative pathways notably by reducing depression and diabetes type 2 risk have not been considered. A population study of 1,193 elderly persons examining depressive symptomatology, caffeine consumption, fasting glucose levels, type 2 diabetes onset, serum amyloid, and factors known to affect cognitive performance was used to explore alternative causal models. Higher caffeine consumption was found to be associated with decreased risk of incident diabetes in men (HR = 0.64; 95% CI 0.42-0.97) and increased risk in women (HR = 1.51; 95% CI 1.08-2.11). No association was found with incident depression. While in the total sample lower ratio Aβ42/Aβ40 levels (OR = 1.36, 95% CI 1.05-1.77, p = 0.02) were found in high caffeine consumers, this failed to reach significance when the analyses were stratified by gender. We found no evidence that reduced risk of cognitive decline in women with high caffeine consumption is moderated or confounded by diabetes or depression. The evidence of an association with plasma beta amyloid could not be clearly demonstrated. Insufficient proof of causal mechanisms currently precludes the recommendation of coffee consumption as a public health measure. Further research should focus on the high estrogen content of coffee as a plausible alternative explanation.

Early respiratory acidosis is a new risk factor for pneumonia after lung resection.

PubMed

Planquette, Benjamin; Le Pimpec-Barthes, Françoise; Trinquart, Ludovic; Meyer, Guy; Riquet, Marc; Sanchez, Olivier

2012-03-01

Postoperative pneumonia (POP) is a life-threatening complication of lung resection (LR). Its risk factors, bacteriological profile and outcome are not well known. The aims of this study were to describe the outcome and causal bacteria and to identify risk factors for POP. We reviewed all cases admitted to intensive care after LR. Clinical parameters, operative and postoperative data were recorded. POP was suspected on the basis of fever, radiographic infiltrate, and either leucocytosis or purulent sputum. The diagnosis was confirmed by culture of a respiratory sample. Risk factors for POP were identified by univariate and multivariate analysis. We included 159 patients in this study. POP was diagnosed in 23 patients (14.4%) and was associated with a higher hospital mortality rate (30% versus 5%, P = 0.0007) and a longer hospital stay. Members of the Enterobacteriaceae and Pseudomonas species were the most frequently identified pathogens. Early respiratory acidosis (ERA; OR, 2.94; 95% CI, 1.1-8.1), blood transfusion (OR, 3.8; 95% CI, 1.1-13.1), bilobectomy (OR, 7.26; 95% CI, 1.2-43.1) and smoking history (OR, 1.84; 95% CI, 1.1-3) were identified as independent risk factors. ERA may be a risk factor for POP and could serve as a target for therapeutic interventions.

Birth weight and mortality: causality or confounding?

PubMed

Basso, Olga; Wilcox, Allen J; Weinberg, Clarice R

2006-08-15

The association between birth weight and mortality is among the strongest seen in epidemiology. While preterm delivery causes both small babies and high mortality, it does not explain this association. Fetal growth restriction has also been proposed, although its features are unclear because it lacks a definition independent of weight. If, as some postulate, birth weight is not itself on the causal path to mortality, its relation with mortality would have to be explained by confounding factors that decrease birth weight and increase mortality. In this paper, the authors explore the characteristics such confounders would require in order to achieve the observed association between birth weight and mortality. Through a simple simulation, they found that the observed steep gradient of risk for small babies at term can be produced by a rare condition or conditions (with a total prevalence of 0.5%) having profound effects on both fetal growth (-1.7 standard deviations) and mortality (relative risk = 160). Candidate conditions might include malformations, fetal or placental aneuploidy, infections, or imprinting disorders. If such rare factors underlie the association of birth weight with mortality, it would have broad implications for the study of fetal growth restriction and birth weight, and for the prevention of infant mortality.

Self-injurious behaviour in people with intellectual disability and autism spectrum disorder.

PubMed

Oliver, Chris; Licence, Lucy; Richards, Caroline

2017-03-01

This review summarises the recent trends in research in the field of self-injurious behaviour in people with intellectual disability and autism spectrum disorder. New data on incidence, persistence and severity add to studies of prevalence to indicate the large scale of the clinical need. A number of person characteristics have been repeatedly identified in prevalence and cohort studies that: can be considered as risk markers (e.g. stereotyped behaviour, autism spectrum disorder) and indicate possible causal mechanisms (e.g. sleep disorder, anxiety). Studies have started to integrate traditional operant learning paradigms with known person characteristics and reviews and meta-analyses of applied behaviour analytic procedures can now inform practice. Despite these positive developments interventions and appropriate support falls far short of the required need. Expansions in applied research are warranted to develop and evaluate innovative service delivery models that can translate knowledge of risk markers and operant learning paradigms into widespread, low cost routine clinical practice. Alongside this, further pure research is needed to elucidate the direction of causality of implicated risk factors, in order to understand and intervene more effectively in self-injury.

Interrupting Intergenerational Cycles of Maternal Obesity

PubMed Central

Gillman, Matthew W.

2016-01-01

Factors operating in the preconception and prenatal periods, such as maternal obesity, excessive gestational weight gain, and gestational diabetes, predict a substantial fraction of childhood obesity as well as lifelong adverse health consequences in the mother. These periods may lend themselves to successful intervention to reduce such risk factors because parents may be especially willing to change behavior if it confers health advantages to their children. If effective interventions started before or during pregnancy can be maintained after birth, they have the potential to lower the risk of both maternal obesity in the next pregnancy and obesity in the growing child, thus helping to interrupt maternal and child inter-generational vicious cycles of obesity, diabetes, and related cardiometabolic health consequences. While this paradigm is appealing, challenges include determining the magnitude, causality, and modifiability of these risk factors, and quantifying any adverse consequences of intervention. PMID:27088333

IQ and schizophrenia in a Swedish national sample: their causal relationship and the interaction of IQ with genetic risk.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Jan; Sundquist, Kristina

2015-03-01

The authors sought to clarify the relationship between IQ and subsequent risk for schizophrenia. IQ was assessed at ages 18-20 in 1,204,983 Swedish males born between 1951 and 1975. Schizophrenia was assessed by hospital diagnosis through 2010. Cox proportional hazards models were used to investigate future risk for schizophrenia in individuals as a function of their IQ score, and then stratified models using pairs of relatives were used to adjust for familial cluster. Finally, regression models were used to examine the interaction between IQ and genetic liability on risk for schizophrenia. IQ had a monotonic relationship with schizophrenia risk across the IQ range, with a mean increase in risk of 3.8% per 1-point decrease in IQ; this association was stronger in the lower than the higher IQ range. Co-relative control analyses showed a similar association between IQ and schizophrenia in the general population and in cousin, half-sibling, and full-sibling pairs. A robust interaction was seen between genetic liability to schizophrenia and IQ in predicting schizophrenia risk. Genetic susceptibility for schizophrenia had a much stronger impact on risk of illness for those with low than high intelligence. The IQ-genetic liability interaction arose largely from IQ differences between close relatives. IQ assessed in late adolescence is a robust risk factor for subsequent onset of schizophrenia. This association is not the result of a declining IQ associated with insidious onset. In this large, representative sample, we found no evidence for a link between genius and schizophrenia. Co-relative control analyses showed that the association between lower IQ and schizophrenia is not the result of shared familial risk factors and may be causal. The strongest effect was seen with IQ differences within families. High intelligence substantially attenuates the impact of genetic liability on the risk for schizophrenia.

Sexual Risk Behavior in Young Adulthood: Broadening the Scope Beyond Early Sexual Initiation

PubMed Central

Epstein, Marina; Bailey, Jennifer A.; Manhart, Lisa E.; Hill, Karl G.; Hawkins, J. David

2013-01-01

A robust link between early sexual initiation and sexual risk-taking behavior is reported in previous studies. The relationship may not be causal, however, as the effect of common risk factors is often not considered. The current study examined whether early initiation is a key predictor of risky sexual behavior in the 20s and 30s, over and above co-occurring individual and environmental factors. Data were drawn from the Seattle Social Development Project, a longitudinal panel of 808 youth. Early predictors (ages 10–15) and sexual risk-taking (ages 21–24 and 30–33) were assessed prospectively. Early sexual initiation (before age 15) was entered into a series of probit regressions that also included family, neighborhood, peer, and individual risk factors. Although a positive bivariate relation between early sexual initiation and sexual risk-taking was observed at both ages, the link did not persist when co-occurring risk factors were included. Behavioral disinhibition and antisocial peer influences emerged as the strongest predictors of sexual risk over and above early sexual initiation. These results suggest that early sexual initiation must be considered in the context of common antecedents; public health policy aimed at delaying sexual intercourse alone is unlikely to substantially reduce sexual risk behavior in young adulthood. PMID:24423058

The maternal-age-associated risk of congenital heart disease is modifiable.

PubMed

Schulkey, Claire E; Regmi, Suk D; Magnan, Rachel A; Danzo, Megan T; Luther, Herman; Hutchinson, Alayna K; Panzer, Adam A; Grady, Mary M; Wilson, David B; Jay, Patrick Y

2015-04-09

Maternal age is a risk factor for congenital heart disease even in the absence of any chromosomal abnormality in the newborn. Whether the basis of this risk resides with the mother or oocyte is unknown. The impact of maternal age on congenital heart disease can be modelled in mouse pups that harbour a mutation of the cardiac transcription factor gene Nkx2-5 (ref. 8). Here, reciprocal ovarian transplants between young and old mothers establish a maternal basis for the age-associated risk in mice. A high-fat diet does not accelerate the effect of maternal ageing, so hyperglycaemia and obesity do not simply explain the mechanism. The age-associated risk varies with the mother's strain background, making it a quantitative genetic trait. Most remarkably, voluntary exercise, whether begun by mothers at a young age or later in life, can mitigate the risk when they are older. Thus, even when the offspring carry a causal mutation, an intervention aimed at the mother can meaningfully reduce their risk of congenital heart disease.

Establishing causality in the decline and deformity of amphibians: The amphibian research and monitoring initiative model

USGS Publications Warehouse

Little, E.E.; Bridges, C.M.; Linder, G.; Boone, M.; ,

2003-01-01

Research to date has indicated that a range of environmental variables such as disease, parasitism, predation, competition, environmental contamination, solar ultraviolet radiation, climate change, or habitat alteration may be responsible for declining amphibian populations and the appearance of deformed organisms, yet in many cases no definitive environmental variable stands out as a causal factor. Multiple Stressors are often present in the habitat, and interactions among these can magnify injury to biota. This raises the possibility that the additive or synergistic impact of these Stressors may be the underlying cause of amphibian declines. Effective management for the restoration of amphibian populations requires the identification of causal factors contributing to their declines. A systematic approach to determine causality is especially important because initial impressions may be misleading or ambiguous. In addition, the evaluation of amphibian populations requires consideration of a broader spatial scale than commonly used in regulatory monitoring. We describe a systematic three-tiered approach to determine causality in amphibian declines and deformities. Tier 1 includes an evaluation of historic databases and extant data and would involve a desktop synopsis of the status of various stressors as well as site visits. Tier 2 studies are iterative, hypothesis driven studies beginning with general tests and continuing with analyses of increasing complexity as certain stressors are identified for further investigation. Tier 3 applies information developed in Tier 2 as predictive indicators of habitats and species at risk over broad landscape scales and provides decision support for the adaptive management of amphibian recovery. This comprehensive, tiered program could provide a mechanistic approach to identifying and addressing specific stressors responsible for amphibian declines across various landscapes.

Causal evidence in risk and policy perceptions: Applying the covariation/mechanism framework.

PubMed

Baucum, Matt; John, Richard

2018-05-01

Today's information-rich society demands constant evaluation of cause-effect relationships; behaviors and attitudes ranging from medical choices to voting decisions to policy preferences typically entail some form of causal inference ("Will this policy reduce crime?", "Will this activity improve my health?"). Cause-effect relationships such as these can be thought of as depending on two qualitatively distinct forms of evidence: covariation-based evidence (e.g., "states with this policy have fewer homicides") or mechanism-based (e.g., "this policy will reduce crime by discouraging repeat offenses"). Some psychological work has examined how people process these two forms of causal evidence in instances of "everyday" causality (e.g., assessing why a car will not start), but it is not known how these two forms of evidence contribute to causal judgments in matters of public risk or policy. Three studies (n = 715) investigated whether judgments of risk and policy scenarios would be affected by covariation and mechanism evidence and whether the evidence types interacted with one another (as suggested by past studies). Results showed that causal judgments varied linearly with mechanism strength and logarithmically with covariation strength, and that the evidence types produced only additive effects (but no interaction). We discuss the results' implications for risk communication and policy information dissemination. Copyright © 2018 Elsevier B.V. All rights reserved.

Bayesian networks improve causal environmental ...

EPA Pesticide Factsheets

Rule-based weight of evidence approaches to ecological risk assessment may not account for uncertainties and generally lack probabilistic integration of lines of evidence. Bayesian networks allow causal inferences to be made from evidence by including causal knowledge about the problem, using this knowledge with probabilistic calculus to combine multiple lines of evidence, and minimizing biases in predicting or diagnosing causal relationships. Too often, sources of uncertainty in conventional weight of evidence approaches are ignored that can be accounted for with Bayesian networks. Specifying and propagating uncertainties improve the ability of models to incorporate strength of the evidence in the risk management phase of an assessment. Probabilistic inference from a Bayesian network allows evaluation of changes in uncertainty for variables from the evidence. The network structure and probabilistic framework of a Bayesian approach provide advantages over qualitative approaches in weight of evidence for capturing the impacts of multiple sources of quantifiable uncertainty on predictions of ecological risk. Bayesian networks can facilitate the development of evidence-based policy under conditions of uncertainty by incorporating analytical inaccuracies or the implications of imperfect information, structuring and communicating causal issues through qualitative directed graph formulations, and quantitatively comparing the causal power of multiple stressors on value

Adverse drug reaction (ADR) occurrence and evaluation in elderly inpatients.

PubMed

Bowman, L; Carlstedt, B C; Hancock, E F; Black, C D

1996-01-01

Determine elderly inpatient's risk ADRs and characterize the events. This is a post-hoc analysis of a comprehensive inpatient ADR survey. Charts were reviewed every four days on all internal medicine service inpatients (1024 patients over four months). Chart review were enhanced by potential indicators such as nurses' and pharmacists' reports; targeted drug orders; 'now', 'stat', and 'hold' orders; off-service physician consults; incident reports; transfers-to-ICU; and abnormal serum drug concentrations. Potential ADRs were classified according to organ system affected, pharmacological type, severity, and Naranjo causality scale. Internal medicine wards of a 350-bed county general hospital. Of 1024 inpatients, 301 were elderly. Overall, 237 patients had an ADR (23%). Elderly patients accounted for 89 (37.5%) of the 237 patients experiencing an ADR. The ADRs experienced by the elderly tended to be more severe (p <0.05) and less idiosyncratic (p <0.05). However, no preferences for organ system (p >0.1) or differences in causality rating (p = 0.25) were detected. When statistically controlled for female gender, renal function and number of drugs, age was no longer a risk factor for ADR occurrence. The elderly experience more ADRs. However, female gender, decline in renal function and polymedicine are the independent factors that account for the elderly's risk. Furthermore, the elderly's ADRs tend to be more severe and an extension of the drug's pharmacology. Therefore, ADR prevention is both important and possible.

Age at Menarche and Time Spent in Education: A Mendelian Randomization Study.

PubMed

Gill, D; Del Greco M, F; Rawson, T M; Sivakumaran, P; Brown, A; Sheehan, N A; Minelli, C

2017-09-01

Menarche signifies the primary event in female puberty and is associated with changes in self-identity. It is not clear whether earlier puberty causes girls to spend less time in education. Observational studies on this topic are likely to be affected by confounding environmental factors. The Mendelian randomization (MR) approach addresses these issues by using genetic variants (such as single nucleotide polymorphisms, SNPs) as proxies for the risk factor of interest. We use this technique to explore whether there is a causal effect of age at menarche on time spent in education. Instruments and SNP-age at menarche estimates are identified from a Genome Wide Association Study (GWAS) meta-analysis of 182,416 women of European descent. The effects of instruments on time spent in education are estimated using a GWAS meta-analysis of 118,443 women performed by the Social Science Genetic Association Consortium (SSGAC). In our main analysis, we demonstrate a small but statistically significant causal effect of age at menarche on time spent in education: a 1 year increase in age at menarche is associated with 0.14 years (53 days) increase in time spent in education (95% CI 0.10-0.21 years, p = 3.5 × 10 -8 ). The causal effect is confirmed in sensitivity analyses. In identifying this positive causal effect of age at menarche on time spent in education, we offer further insight into the social effects of puberty in girls.

A new approach to hierarchical data analysis: Targeted maximum likelihood estimation for the causal effect of a cluster-level exposure.

PubMed

Balzer, Laura B; Zheng, Wenjing; van der Laan, Mark J; Petersen, Maya L

2018-01-01

We often seek to estimate the impact of an exposure naturally occurring or randomly assigned at the cluster-level. For example, the literature on neighborhood determinants of health continues to grow. Likewise, community randomized trials are applied to learn about real-world implementation, sustainability, and population effects of interventions with proven individual-level efficacy. In these settings, individual-level outcomes are correlated due to shared cluster-level factors, including the exposure, as well as social or biological interactions between individuals. To flexibly and efficiently estimate the effect of a cluster-level exposure, we present two targeted maximum likelihood estimators (TMLEs). The first TMLE is developed under a non-parametric causal model, which allows for arbitrary interactions between individuals within a cluster. These interactions include direct transmission of the outcome (i.e. contagion) and influence of one individual's covariates on another's outcome (i.e. covariate interference). The second TMLE is developed under a causal sub-model assuming the cluster-level and individual-specific covariates are sufficient to control for confounding. Simulations compare the alternative estimators and illustrate the potential gains from pairing individual-level risk factors and outcomes during estimation, while avoiding unwarranted assumptions. Our results suggest that estimation under the sub-model can result in bias and misleading inference in an observational setting. Incorporating working assumptions during estimation is more robust than assuming they hold in the underlying causal model. We illustrate our approach with an application to HIV prevention and treatment.

The role of respiratory tract infections and the microbiome in the development of asthma: A narrative review.

PubMed

van Meel, Evelien R; Jaddoe, Vincent W V; Bønnelykke, Klaus; de Jongste, Johan C; Duijts, Liesbeth

2017-10-01

Asthma is a common disease in childhood, and might predispose for chronic obstructive respiratory morbidity in adolescence and adulthood. Various early-life risk factors might influence the risk of wheezing, asthma, and lower lung function in childhood. Cohort studies demonstrated that lower respiratory tract infections in the first years of life are associated with an increased risk of wheezing and asthma, while the association with lung function is less clear. Additionally, the gut and airway microbiome might influence the risk of wheezing and asthma. The interaction between respiratory tract infections and the microbiome complicates studies of their associations with wheezing, asthma, and lung function. Furthermore, the causality behind these observations is still unclear, and several other factors such as genetic susceptibility and the immune system might be of importance. This review is focused on the association of early-life respiratory tract infections and the microbiome with wheezing, asthma, and lung function, it is possible influencing factors and perspectives for future studies. © 2017 Wiley Periodicals, Inc.

Mental Models of Cause and Inheritance for Type 2 Diabetes Among Unaffected Individuals Who Have a Positive Family History.

PubMed

Daack-Hirsch, Sandra; Shah, Lisa L; Cady, Alyssa D

2018-03-01

Using the familial risk perception (FRP) model as a framework, we elicited causal and inheritance explanations for type 2 diabetes (T2D) from people who do not have T2D but have a family history for it. We identified four composite mental models for cause of T2D: (a) purely genetic; (b) purely behavioral/environmental; (c) direct multifactorial, in which risk factors interact and over time directly lead to T2D; and (d) indirect multifactorial, in which risk factors interact and over time cause a precursor health condition (such as obesity or metabolic syndrome) that leads to T2D. Interestingly, participants described specific risk factors such as genetics, food habits, lifestyle, weight, and culture as "running in the family." Our findings provide insight into lay beliefs about T2D that can be used by clinicians to anticipate or make sense of responses to questions they pose to patients about mental models for T2D.

Elder abuse in Chinese populations: a global review.

PubMed

Dong, XinQi

2015-01-01

This review focuses on the epidemiology of elder abuse in the global Chinese population with respect to its prevalence, risk factors, and consequences, as well as the perceptions of elder abuse. Evidence revealed that elder abuse and its subtypes are common among the global Chinese population with prevalence ranging from 0.2% to 64%. Younger age, lower income levels, depression, cognitive impairment, and lack of social support were consistently associated with self-reported elder abuse. Caregiver burden was a constant risk factor for the proclivity to elder abuse by caregivers. The adverse health outcomes of elder abuse included suicidal ideation and psychological stress. Some primary research gaps exist: such as, lack of consistency in measurements and recall periods, insufficient studies on the causal relationships between potential risk factors and elder abuse, consequences of elder abuse, and possible interventions. In order to reduce the risk of elder abuse in the global Chinese population, collaboration is encouraged among researchers, health care professionals, social service providers, and policy makers.

A System Dynamics Model for Planning Cardiovascular Disease Interventions

PubMed Central

Homer, Jack; Evans, Elizabeth; Zielinski, Ann

2010-01-01

Planning programs for the prevention and treatment of cardiovascular disease (CVD) is a challenge to every community that wants to make the best use of its limited resources. Selecting programs that provide the greatest impact is difficult because of the complex set of causal pathways and delays that link risk factors to CVD. We describe a system dynamics simulation model developed for a county health department that incorporates and tracks the effects of those risk factors over time on both first-time and recurrent events. We also describe how the model was used to evaluate the potential impacts of various intervention strategies for reducing the county's CVD burden and present the results of those policy tests. PMID:20167899

The growing prevalence of kidney stones and opportunities for prevention.

PubMed

Richman, Katherine; O'Bell, John; Pareek, Gyan

2014-12-02

The prevalence of kidney stones is climbing in the United States. Several investigators have demonstrated an association between metabolic syndrome and kidney stones and some have proposed a causal link. Risk factors for nephrolithiasis can be identified with a 24-hour urine collection and preventive measures can be customized to meet the needs of individual patients. Dietary and pharmacologic interventions are available to address urinary risk factors such as inadequate urine volume, hypercalcuria, hyperoxaluria, hyperuricosuria and hypocitraturia. Given that morbidity and healthcare costs associated with nephrolithiasis are on the rise, deterring stone formation is increasingly important. Multidisciplinary clinics that foster collaboration between urologists, nephrologists and dieticians offer patients effective prevention and treatment strategies.

[Causal "cancer personality" attribution--an expression of maladaptive coping with illness?].

PubMed

Faller, H; Lang, H; Schilling, S

1996-01-01

In psycho-oncology, the concept of a "cancer-prone personality" has gained some attention. This notion means that persons who try to stay pseudo-normal in spite of severe life stress, suppress negative emotions, particularly anger, and sacrifice themselves for other people without uttering any personal demands, are at a high risk to develop cancer. However, it has been demonstrated by previous research that features of the cancer-prone personality could only be found if the ill person was convinced to suffer from cancer, irrespective of what the factual diagnosis was. Thus it can be concluded that at least some aspects of the so called cancer personality might be the results of coping with the belief of having cancer. The present study had the objective to describe causal attributions to psychosocial factors in cancer patients, and to find out if these were connected with emotional state and coping. N = 120 newly diagnosed lung cancer patients were included in the study. The instruments consisted of a semi-structured interview, a check-list of subjective causal factors, self-reports and interviewer ratings on emotional state and standardised questionnaires about depression and coping. Patients who made a psychosocial causal attribution proved to suffer from greater emotional distress, to be more depressed and less hopeful than other patients. This difference seemed to be mediated by a depressive way of coping with the illness (brooding, wrangling). Thus, an attribution of the illness to psychological factors seems indicative of a maladaptive way of coping with illness. This result is supported by similar findings of previous research. The question is put up to discussion if the psychosomatic concept of a cancer personality may reflect patients' subjective theories which in turn may be the expression of their depressive coping modes.

An exploration of the factor structure and development of potentially useful subscales of etiological beliefs about schizophrenia in a general population sample.

PubMed

Goulding, Sandra M; Broussard, Beth; Demir, Berivan; Compton, Michael T

2009-11-01

Given that accessing care, treatment engagement, and course and outcomes among people with schizophrenia may be influenced by beliefs about causes in the larger community, causal beliefs about schizophrenia have been studied in numerous communities around the world. In particular, the 30-item list of etiological attributions developed by Angermeyer and colleagues has been used to describe causal beliefs in patients, family members, and lay community members within such communities. The current study, the first examination of the latent or factorial structure of these 30 causal beliefs, seeks to provide informative subscales that may enhance reliability and validity of groupings of causes for future analyses involving community members. Data were gathered from six separate surveys involving three distinct groups of individuals from the same community within the southeastern United States: lay community members, relatives of individuals with schizophrenia-spectrum disorders, and police officers at the start of a 1-week mental health training program. Exploratory factor analysis in the overall sample (n=577) revealed four factors that were used to define four subscales, termed: personal/family/social stressors (14 items), inconsistent with modern conceptions of risk (8 items), external/environmental insults to the brain (6 items), and consistent with modern biological conceptions (2 items). Cronbach's internal consistency reliability coefficients for these subscales were 0.91, 0.83, 0.71, and 0.65, respectively. These findings suggest that subscales could be derived to provide continuous measures for assessing causal beliefs in order to study how this concept relates to attitudes toward schizophrenia, the people affected by the disorder, and treatments that are recommended by mental health professionals. Replication within similar and dissimilar groups is warranted.

Investigating genetic correlations and causal effects between caffeine consumption and sleep behaviours.

PubMed

Treur, Jorien L; Gibson, Mark; Taylor, Amy E; Rogers, Peter J; Munafò, Marcus R

2018-04-22

Observationally, higher caffeine consumption is associated with poorer sleep and insomnia. We investigated whether these associations are a result of shared genetic risk factors and/or (possibly bidirectional) causal effects. Summary-level data were available from genome-wide association studies on caffeine intake (n = 91 462), plasma caffeine and caffeine metabolic rate (n = 9876), sleep duration and chronotype (being a "morning" versus an "evening" person) (n = 128 266), and insomnia complaints (n = 113 006). First, genetic correlations were calculated, reflecting the extent to which genetic variants influencing caffeine consumption and those influencing sleep overlap. Next, causal effects were estimated with bidirectional, two-sample Mendelian randomization. This approach utilizes the genetic variants most robustly associated with an exposure variable as an "instrument" to test causal effects. Estimates from individual variants were combined using inverse-variance weighted meta-analysis, weighted median regression and MR-Egger regression. We found no clear evidence for a genetic correlation between caffeine intake and sleep duration (rg = 0.000, p = .998), chronotype (rg = 0.086, p = .192) or insomnia complaints (rg = -0.034, p = .700). For plasma caffeine and caffeine metabolic rate, genetic correlations could not be calculated because of the small sample size. Mendelian randomization did not support causal effects of caffeine intake on sleep, or vice versa. There was weak evidence that higher plasma caffeine levels causally decrease the odds of being a morning person. Although caffeine may acutely affect sleep when taken shortly before bedtime, our findings suggest that a sustained pattern of high caffeine consumption is more likely to be associated with poorer sleep through shared environmental factors. Future research should identify such environments, which could aid the development of interventions to improve sleep. © 2018 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment?

PubMed Central

Teschke, Rolf; Schulze, Johannes; Eickhoff, Axel; Danan, Gaby

2017-01-01

Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can confound the DILI diagnosis. Searching for alternative causes is a key element of RUCAM (Roussel Uclaf Causality Assessment Method) to assess rigorously causality in suspected DILI cases. Diagnostic biomarkers as blood tests would be a great help to clinicians, regulators, and pharmaceutical industry would be more comfortable if, in addition to RUCAM, causality of DILI can be confirmed. High specificity and sensitivity are required for any diagnostic biomarker. Although some risk factors are available to evaluate liver safety of drugs in patients, no valid diagnostic or prognostic biomarker exists currently for idiosyncratic DILI when a liver injury occurred. Identifying a biomarker in idiosyncratic DILI requires detailed knowledge of cellular and biochemical disturbances leading to apoptosis or cell necrosis and causing leakage of specific products in blood. As idiosyncratic DILI is typically a human disease and hardly reproducible in animals, pathogenetic events and resulting possible biomarkers remain largely undisclosed. Potential new diagnostic biomarkers should be evaluated in patients with DILI and RUCAM-based established causality. In conclusion, causality assessment in cases of suspected idiosyncratic DILI is still best achieved using RUCAM since specific biomarkers as diagnostic blood tests that could enhance RUCAM results are not yet available. PMID:28398242

Financial strain and cancer risk behaviors among African Americans.

PubMed

Advani, Pragati S; Reitzel, Lorraine R; Nguyen, Nga T; Fisher, Felicia D; Savoy, Elaine J; Cuevas, Adolfo G; Wetter, David W; McNeill, Lorna H

2014-06-01

African Americans suffer disproportionately from the adverse consequences of behavioral risk factors for cancer relative to other ethnic groups. Recent studies have assessed how financial strain might uniquely contribute to engagement in modifiable behavioral risk factors for cancer, but not among African Americans. The current study examined associations between financial strain and modifiable cancer risk factors (smoking, at-risk alcohol use, overweight/obesity, insufficient physical activity, inadequate fruit and vegetable intake, and multiple risk factors) among 1,278 African American adults (age, 46.5 ± 12.6 years; 77% female) and explored potential mediators (stress and depressive symptoms) of those associations. Logistic regression models were used to examine associations between financial strain and cancer risk factors. Analyses were adjusted for age, sex, partner status, income, educational level, and employment status. Analyses involving overweight/obesity status additionally controlled for fruit and vegetable intake and physical activity. Nonparametric bootstrapping procedures were used to assess mediation. Greater financial strain was associated with greater odds of insufficient physical activity (P < 0.003) and smoking (P = 0.005) and was positively associated with the total number of cancer risk factors (P < 0.0001). There was a significant indirect effect of both stress and depressive symptoms on the relations of financial strain with physical inactivity and multiple risk factors, respectively. Future interventions aimed at reducing cancer disparities should focus on African Americans experiencing higher financial strain while addressing their stress and depressive symptoms. Longitudinal studies are needed to assess the temporal and causal relations between financial strain and modifiable behavioral cancer risk factors among African Americans. ©2014 American Association for Cancer Research.

THE ORIGINS OF COGNITIVE DEFICITS IN VICTIMIZED CHILDREN: IMPLICATIONS FOR NEUROSCIENTISTS AND CLINICIANS

PubMed Central

Danese, Andrea; Moffitt, Terrie E; Arseneault, Louise; Bleiberg, Ben A; Dinardo, Perry B; Gandelman, Stephanie B; Houts, Renate; Ambler, Antony; Fisher, Helen; Poulton, Richie; Caspi, Avshalom

2016-01-01

OBJECTIVE Individuals reporting a history of childhood violence victimization have impaired brain function. However, the clinical significance, reproducibility, and causality of these findings are disputed. We directly tested these research gaps. METHOD We tested the association between prospectively-collected measures of childhood violence victimization and cognitive functions in childhood, adolescence, and adulthood among 2,232 members of the UK E-Risk Study and 1,037 members of the New Zealand Dunedin Study, who were followed-up from birth until ages 18 and 38 years, respectively. We used multiple measures of victimization and cognition, and included comparisons of cognitive scores for twins discordant for victimization. RESULTS We found that individuals exposed to childhood victimization had pervasive impairments in clinically-relevant cognitive functions including general intelligence, executive function, processing speed, memory, perceptual reasoning, and verbal comprehension in adolescence and adulthood. However, the observed cognitive deficits in victimized individuals were largely explained by cognitive deficits that predated childhood victimization and by confounding genetic and environmental risks. CONCLUSIONS Findings from two population-representative birth cohorts totaling more than 3,000 individuals and born 20 years and 20,000 kilometers apart suggest that the association between childhood violence victimization and later cognition is largely non-causal, in contrast to conventional interpretations. These findings urge adopting a more circumspect approach to causal inference in the neuroscience of stress. Clinically, cognitive deficits should be conceptualized as individual risk factors for victimization as well as potential complicating features during treatment. PMID:27794691

[Malignant mesothelioma risk factors: experience in the General Hospital of Mexico].

PubMed

Hernández-Solís, Alejandro; Garcia-Hernández, Cyntia; Reding-Bernal, Arturo; Cruz-Ortiz, Humberto; Cicero-Sabido, Raúl

2013-01-01

Malignant mesothelioma is a neoplasm of bad prognosis, it is linked with asbestos contact, but there are cases without this antecedent. To investigate the relationship of asbestos exposition and other factors with malignant mesothelioma. Retrospective analysis of histologic confirmed cases of malignant mesothelioma, neoplasic familiar history, tobacco smoking, exposure to wood smoke and to asbestos, were annotated in a paired case/control study 1: 1-3 with logistic regression model to identify risk factors for OR. 61 cases of malignant mesothelioma were confirmed by histopathologic study, 41 male and 20 female. Mean age was 56 years ± 13 years; 56 cases (91.8%) correspond to epithelial malignant mesothelioma, three sarcomatous (4.9%) one desmoplastic and one biphasic. One in eight (13.1%) had exposure to asbestos. Model of logistic regression with four variables: history of familiar cancer, tobacco smoking, wood smoke and asbestos exposition, the the last one with an OR= 3.083 and p > 0.05. No other variables found to be a risk factor for malignant mesothelioma. Exposure to asbestos is a risk factor for malignant mesothelioma, which is confirmed in this study, however it is important to extend the investigation of other possible causal factors of this disease.

A review of cognitive biases in youth depression: attention, interpretation and memory.

PubMed

Platt, Belinda; Waters, Allison M; Schulte-Koerne, Gerd; Engelmann, Lina; Salemink, Elske

2017-04-01

Depression is one of the most common mental health problems in childhood and adolescence. Although data consistently show it is associated with self-reported negative cognitive styles, less is known about the mechanisms underlying this relationship. Cognitive biases in attention, interpretation and memory represent plausible mechanisms and are known to characterise adult depression. We provide the first structured review of studies investigating the nature and causal role of cognitive biases in youth depression. Key questions are (i) do cognitive biases characterise youth depression? (ii) are cognitive biases a vulnerability factor for youth depression? and (iii) do cognitive biases play a causal role in youth depression? We find consistent evidence for positive associations between attention and interpretation biases and youth depression. Stronger biases in youth with an elevated risk of depression support cognitive-vulnerability models. Preliminary evidence from cognitive bias modification paradigms supports a causal role of attention and interpretation biases in youth depression but these paradigms require testing in clinical samples before they can be considered treatment tools. Studies of memory biases in youth samples have produced mixed findings and none have investigated the causal role of memory bias. We identify numerous areas for future research in this emerging field.

Exploring the relationship between child physical abuse and adult dating violence using a causal inference approach in an emerging adult population in South Korea.

PubMed

Jennings, Wesley G; Park, MiRang; Richards, Tara N; Tomsich, Elizabeth; Gover, Angela; Powers, Ráchael A

2014-12-01

Child maltreatment is one of the most commonly examined risk factors for violence in dating relationships. Often referred to as the intergenerational transmission of violence or cycle of violence, a fair amount of research suggests that experiencing abuse during childhood significantly increases the likelihood of involvement in violent relationships later, but these conclusions are primarily based on correlational research designs. Furthermore, the majority of research linking childhood maltreatment and dating violence has focused on samples of young people from the United States. Considering these limitations, the current study uses a rigorous, propensity score matching approach to estimate the causal effect of experiencing child physical abuse on adult dating violence among a large sample of South Korean emerging adults. Results indicate that the link between child physical abuse and adult dating violence is spurious rather than causal. Study limitations and implications are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biological causal links on physiological and evolutionary time scales.

PubMed

Karmon, Amit; Pilpel, Yitzhak

2016-04-26

Correlation does not imply causation. If two variables, say A and B, are correlated, it could be because A causes B, or that B causes A, or because a third factor affects them both. We suggest that in many cases in biology, the causal link might be bi-directional: A causes B through a fast-acting physiological process, while B causes A through a slowly accumulating evolutionary process. Furthermore, many trained biologists tend to consistently focus at first on the fast-acting direction, and overlook the slower process in the opposite direction. We analyse several examples from modern biology that demonstrate this bias (codon usage optimality and gene expression, gene duplication and genetic dispensability, stem cell division and cancer risk, and the microbiome and host metabolism) and also discuss an example from linguistics. These examples demonstrate mutual effects between the fast physiological processes and the slow evolutionary ones. We believe that building awareness of inference biases among biologists who tend to prefer one causal direction over another could improve scientific reasoning.

Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children – a prospective observational cohort study of 6,601 admissions

PubMed Central

2013-01-01

Background Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors. Methods We undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis. Results A total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60). Conclusions ADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short-stay surgeries. PMID:24228998

New Onset Autoimmune Hepatitis during Anti-Tumor Necrosis Factor-Alpha Treatment in Children.

PubMed

Ricciuto, Amanda; Kamath, Binita M; Walters, Thomas D; Frost, Karen; Carman, Nicholas; Church, Peter C; Ling, Simon C; Griffiths, Anne M

2018-03-01

To evaluate a large anti-tumor necrosis factor (TNF)-treated pediatric inflammatory bowel disease cohort for drug-induced liver injury (DILI) following presentation of an index case with suspected DILI with autoimmune features after infliximab exposure. To characterize the incidence, natural history, and risk factors for liver enzyme elevation with anti-TNF use. We reviewed the index case and performed a retrospective cohort study of 659 children receiving anti-TNF therapy between 2000 and 2015 at a tertiary pediatric inflammatory bowel disease center. Patients with alanine aminotransferase (ALT) ≥×2 the upper limit of normal were included. The incidence, evolution, and risk factors for liver injury were examined with univariate and multivariable proportional hazards regression. Causality was assessed using the Roussel-Uclaf Causality Assessment Method. The index case, a teenage girl with Crohn's disease, developed elevated liver enzymes and features of autoimmune hepatitis on liver biopsy 23 weeks after starting infliximab. The injury resolved entirely within 4 months of withdrawing infliximab without additional therapy. Overall, 7.7% of our cohort developed new ALT elevations while on anti-TNF. Most ALT elevations were mild and transient and attributable to alternate etiologies. No additional clear cases of autoimmune hepatitis were identified. Transient liver enzyme abnormalities are relatively common among anti-TNF-treated children. Anti-TNF-related DILI with autoimmune features is rare but must be recognized so that therapy can be stopped. Copyright © 2017 Elsevier Inc. All rights reserved.

Bayesian networks improve causal environmental assessments for evidence-based policy

EPA Science Inventory

Rule-based weight of evidence approaches to ecological risk assessment may not account for uncertainties and generally lack probabilistic integration of lines of evidence. Bayesian networks allow causal inferences to be made from evidence by including causal knowledge about the p...

A systematic review of the risks factors associated with the onset and natural progression of hydrocephalus.

PubMed

Walsh, Stephanie; Donnan, Jennifer; Morrissey, Andrea; Sikora, Lindsey; Bowen, Sonya; Collins, Kayla; MacDonald, Don

2017-07-01

The purpose of this study was to systematically assess and synthesize the world literature on risk factors for the onset and natural progression of hydrocephalus, thereby providing a basis for policy makers to identify appropriate risk management measures to mitigate the burden of disease in Canada. Evidence for risk factors was limited for both onset and progression. Two meta-analyses that examined a risk factor for onset met the inclusion criteria. One found a significant protective effect of prenatal vitamins among case control studies, but not cohort/randomized controlled trials (RCTs). The second found maternal obesity to be a significant risk factor for congenital hydrocephalus. Significant risk factors among 25 observational studies included: biological (multiple births, maternal parity, common cold with fever, maternal thyroid disease, family history, preterm birth, hypertension, ischemic heart disease, ischemic ECG changes, higher cerebrospinal fluid protein concentration following vestibular schwannoma); lifestyle (maternal obesity, high-density lipoprotein (HDL) cholesterol, maternal diabetes, maternal age), healthcare-related (caesarean section, interhospital transfer, drainage duration following subarachnoid hemorrhage, proximity to midline for craniectomy following traumatic brain injury); pharmaceutical (prenatal exposure to: tribenoside, metronidazole, anesthesia, opioids); and environmental (altitude, paternal occupation). Three studies reported on genetic risk factors: no significant associations were found. There are major gaps in the literature with respect to risk factors for the natural progression of hydrocephalus. Only two observational studies were included and three factors reported. Many risk factors for the onset of hydrocephalus have been studied; for most, evidence remains limited or inconclusive. More work is needed to confirm any causal associations and better inform policy. Copyright © 2016. Published by Elsevier B.V.

Probabilistic Causal Analysis for System Safety Risk Assessments in Commercial Air Transport

NASA Technical Reports Server (NTRS)

Luxhoj, James T.

2003-01-01

Aviation is one of the critical modes of our national transportation system. As such, it is essential that new technologies be continually developed to ensure that a safe mode of transportation becomes even safer in the future. The NASA Aviation Safety Program (AvSP) is managing the development of new technologies and interventions aimed at reducing the fatal aviation accident rate by a factor of 5 by year 2007 and by a factor of 10 by year 2022. A portfolio assessment is currently being conducted to determine the projected impact that the new technologies and/or interventions may have on reducing aviation safety system risk. This paper reports on advanced risk analytics that combine the use of a human error taxonomy, probabilistic Bayesian Belief Networks, and case-based scenarios to assess a relative risk intensity metric. A sample case is used for illustrative purposes.

Hearing loss among older construction workers: Updated analyses.

PubMed

Dement, John; Welch, Laura S; Ringen, Knut; Cranford, Kim; Quinn, Patricia

2018-04-01

A prior study of this construction worker population found significant noise-associated hearing loss. This follow-up study included a much larger study population and consideration of additional risk factors. Data included audiometry, clinical chemistry, personal history, and work history. Qualitative exposure metrics for noise and solvents were developed. Analyses compared construction workers to an internal reference group with lower exposures and an external worker population with low noise exposure. Among participants (n = 19 127) an overall prevalence of hearing loss of 58% was observed, with significantly increased prevalence across all construction trades. Construction workers had significantly increased risk of hearing loss compared to reference populations, with increasing risk by work duration. Noise exposure, solvent exposure, hypertension, and smoking were significant risk factors in multivariate models. Results support a causal relationship between construction trades work and hearing loss. Prevention should focus on reducing exposure to noise, solvents, and cigarette smoke. © 2018 Wiley Periodicals, Inc.

HIV prevention for South African youth: which interventions work? A systematic review of current evidence

PubMed Central

2010-01-01

Background In South Africa, HIV prevalence among youth aged 15-24 is among the world's highest. Given the urgent need to identify effective HIV prevention approaches, this review assesses the evidence base for youth HIV prevention in South Africa. Methods Systematic, analytical review of HIV prevention interventions targeting youth in South Africa since 2000. Critical assessment of interventions in 4 domains: 1) study design and outcomes, 2) intervention design (content, curriculum, theory, adaptation process), 3) thematic focus and HIV causal pathways, 4) intervention delivery (duration, intensity, who, how, where). Results Eight youth HIV prevention interventions were included; all were similar in HIV prevention content and objectives, but varied in thematic focus, hypothesised causal pathways, theoretical basis, delivery method, intensity and duration. Interventions were school- (5) or group-based (3), involving in- and out-of-school youth. Primary outcomes included HIV incidence (2), reported sexual risk behavior alone (4), or with alcohol use (2). Interventions led to reductions in STI incidence (1), and reported sexual or alcohol risk behaviours (5), although effect size varied. All but one targeted at least one structural factor associated with HIV infection: gender and sexual coercion (3), alcohol/substance use (2), or economic factors (2). Delivery methods and formats varied, and included teachers (5), peer educators (5), and older mentors (1). School-based interventions experienced frequent implementation challenges. Conclusions Key recommendations include: address HIV social risk factors, such as gender, poverty and alcohol; target the structural and institutional context; work to change social norms; and engage schools in new ways, including participatory learning. PMID:20187957

Practical Management of Pressure Sores

PubMed Central

Jordan, John M.

1992-01-01

Pressure sores are common in the debilitated elderly. Causal factors are unrelieved pressure, shearing forces, friction, and moisture. Preventive measures should be used for all high-risk patients, defined by general condition, mental status, degree of incontinence, amount of activity, and mobility. Principles of treating ulcers include pressure relief, reducing bacterial counts, debriding necrotic tissue, and providing a moist, clean environment. Imagesp2385-ap2389-ap2392-a PMID:21221298

Do insulin-like growth factors mediate the effect of alcohol on breast cancer risk?

PubMed

Yu, H; Berkel, J

1999-06-01

Despite a large number of epidemiologic studies demonstrating an increased risk of breast cancer in association with alcohol consumption, a causal relationship between alcohol intake and breast cancer risk remains to be determined. Several biological mechanisms have been proposed, but none of them explains well the features of the association, i.e. a modest increase in risk, a limited range of dose-response relationship and no further increase in risk among heavy drinkers. A new mechanism underlying a possible biological role of alcohol in breast cancer is proposed in this paper. Moderate consumption of alcohol increases the production of insulin-like growth factors (IGFs) by the liver and elevated IGFs via circulation stimulate or promote the development and/or growth of breast cancer. The effect of alcohol on IGF production declines among heavy drinkers as alcohol-caused liver-function damage results in no further increase in IGF production. Therefore, compared to moderate drinkers, heavy alcohol users do not have a higher risk of breast cancer.

[Patent foramen ovale and decompression illness in divers].

PubMed

Sivertsen, Wiebke; Risberg, Jan; Norgård, Gunnar

2010-04-22

About 25 % of the population has patent foramen ovale, and the condition has been assumed to be a causal factor in decompressive illness. Transcatheter closure is possible and is associated with a relatively low risk, but it has not been clarified whether there is an indication for assessment and treatment of the condition in divers. The present study explored a possible relationship between a patent foramen ovale and the risk for decompression illness in divers, if there are categories of divers that should be screened for the condition and what advice should be given to divers with this condition. The review is based on literature identified through a search in Pubmed and the authors' long clinical experience in the field. The risk of decompression illness for divers with a persistent foramen ovale is about five times higher than that in divers without this condition, but the absolute risk for decompression illness is only 2.5 after 10,000 dives. A causal association has not been shown between patent foramen ovale and decompression illness. Even if closure of patent foramen ovale may be done with relatively small risk, the usefulness of the procedure has not been documented in divers. We do not recommend screening for patent foramen ovale in divers because the absolute risk of decompression illness is small and transcatheter closure is only indicated after decompression illness in some occupational divers.

Tumor Secreted Autocrine Motility Factor (AMF): Causal Role in an Animal Model of Cachexia

DTIC Science & Technology

2005-08-01

AD Award Number: DAMD17-02-1-0586 TITLE: Tumor Secreted Autocrine Motility Factor ( AMF ): Causal Role in an Animal Model of Cachexia PRINCIPAL...5a. CONTRACT NUMBER Tumor Secreted Autocrine Motility Factor ( AMF ): Causal Role in an Animal Model of Cachexia 5b. GRANT NUMBER DAM D1 7-02-1-0586 5c...quality of life and postpone mortality. We proposed that autocrine motility factor ( AMF ) is released into the bloodstream from cancer sites and

Risk Factors for Neck and Upper Extremity Disorders among Computers Users and the Effect of Interventions: An Overview of Systematic Reviews

PubMed Central

Andersen, Johan H.; Fallentin, Nils; Thomsen, Jane F.; Mikkelsen, Sigurd

2011-01-01

Background To summarize systematic reviews that 1) assessed the evidence for causal relationships between computer work and the occurrence of carpal tunnel syndrome (CTS) or upper extremity musculoskeletal disorders (UEMSDs), or 2) reported on intervention studies among computer users/or office workers. Methodology/Principal Findings PubMed, Embase, CINAHL and Web of Science were searched for reviews published between 1999 and 2010. Additional publications were provided by content area experts. The primary author extracted all data using a purpose-built form, while two of the authors evaluated the quality of the reviews using recommended standard criteria from AMSTAR; disagreements were resolved by discussion. The quality of evidence syntheses in the included reviews was assessed qualitatively for each outcome and for the interventions. Altogether, 1,349 review titles were identified, 47 reviews were retrieved for full text relevance assessment, and 17 reviews were finally included as being relevant and of sufficient quality. The degrees of focus and rigorousness of these 17 reviews were highly variable. Three reviews on risk factors for carpal tunnel syndrome were rated moderate to high quality, 8 reviews on risk factors for UEMSDs ranged from low to moderate/high quality, and 6 reviews on intervention studies were of moderate to high quality. The quality of the evidence for computer use as a risk factor for CTS was insufficient, while the evidence for computer use and UEMSDs was moderate regarding pain complaints and limited for specific musculoskeletal disorders. From the reviews on intervention studies no strong evidence based recommendations could be given. Conclusions/Significance Computer use is associated with pain complaints, but it is still not very clear if this association is causal. The evidence for specific disorders or diseases is limited. No effective interventions have yet been documented. PMID:21589875

The Mental Health Outcomes of Drought: A Systematic Review and Causal Process Diagram

PubMed Central

Vins, Holly; Bell, Jesse; Saha, Shubhayu; Hess, Jeremy J.

2015-01-01

Little is understood about the long term, indirect health consequences of drought (a period of abnormally dry weather). In particular, the implications of drought for mental health via pathways such as loss of livelihood, diminished social support, and rupture of place bonds have not been extensively studied, leaving a knowledge gap for practitioners and researchers alike. A systematic review of literature was performed to examine the mental health effects of drought. The systematic review results were synthesized to create a causal process diagram that illustrates the pathways linking drought effects to mental health outcomes. Eighty-two articles using a variety of methods in different contexts were gathered from the systematic review. The pathways in the causal process diagram with greatest support in the literature are those focusing on the economic and migratory effects of drought. The diagram highlights the complexity of the relationships between drought and mental health, including the multiple ways that factors can interact and lead to various outcomes. The systematic review and resulting causal process diagram can be used in both practice and theory, including prevention planning, public health programming, vulnerability and risk assessment, and research question guidance. The use of a causal process diagram provides a much needed avenue for integrating the findings of diverse research to further the understanding of the mental health implications of drought. PMID:26506367

Estimating the causal effects of smoking.

PubMed

Rubin, D B

An important application of statistics in recent years has been to address the causal effects of smoking. There is little doubt that there are health risks associated with smoking. However, more general issues concern the causal effects due to the alleged misconduct of the tobacco industry or due to programmes designed to curtail tobacco use. To address any such causal question, assumptions must be made. Although some of the issues are well known in the statistical and epidemiological literature, there does not appear to be a unified treatment that provides prescriptive guidance on the estimation of these causal effects with explication of the needed assumptions. A 'conduct attributable fraction' is derived, which allows for arbitrary changes in smoking and non-smoking health care expenditure related factors in a counterfactual world without the alleged misconduct, and therefore generalizes the traditional 'smoking attributable fraction'. The formulation presented here, although described for the problem of estimating excess health care expenditures due to the alleged misconduct of the tobacco industry, is more general. It can be applied to any outcome, such as mortality, morbidity, or income from excise taxes, as well as to any situation in which consequences due to alleged misconduct (for example, of two entities, such as the tobacco and the asbestos industries) or due to hypothetical programmes (for example, extra smoking reduction initiatives) are to be estimated. Copyright 2001 John Wiley & Sons, Ltd.

Genetics of coronary artery disease: discovery, biology and clinical translation

PubMed Central

Khera, Amit V.; Kathiresan, Sekar

2018-01-01

Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked about 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forward, genetic testing could enable precision medicine approaches, by identifying subgroups of patients at increased risk of CAD or those with a specific driving pathophysiology in whom a therapeutic or preventive approach is most useful. PMID:28286336

Participation in Athletics and Female Sexual Risk Behavior: The Evaluation of Four Causal Structures.

ERIC Educational Resources Information Center

Dodge, Tonya; Jaccard, James

2002-01-01

Compared sexual risk behavior of female athletes and nonathletes. Examined mediation, reverse mediation, spurious effects, and moderated causal models, using as potential mediators physical development, educational aspirations, self-esteem, attitudes toward pregnancy, involvement in a romantic relationship, age, ethnicity, and social class. Found…

Risk factors for fishermen's health and safety in Greece.

PubMed

Frantzeskou, Elpida; Kastania, Anastasia N; Riza, Elena; Jensen, Olaf C; Linos, Athena

2012-01-01

This is, to the best of our knowledge, the first occupational health study in Greek fishing. The aim of the study is to determine the risks for health and safety in Greek fisheries workers by exploring their health status and the health risk factors present in their occupational environment, thus providing a current baseline for further research in the future and for documentation of the needs for prevention. A questionnaire pilot study was carried out in a random sample of 100 Greek fishermen. Twenty-eight per cent (28%) had experienced at least one injury, of which half caused more than one day absence, while 14% had a near drowning experience. The health risks factors studied include excessive weight, cardiovascular incidents and dermatological, musculoskeletal, respiratory, hearing, stress, and anxiety problems. The occupational health risk factors include alcohol, fatty food consumption, smoking, and lack of physical exercise. The health effects observed are causally related to diet, smoking, and exercise, which in turn relate to the specific working conditions and culture in small-scale fishing that need to be taken into consideration in prevention programmes. The results are comparable with international fisheries experience, mainly from Poland, Denmark, and Turkey.

Academic Success Factors: An IT Student Perspective

ERIC Educational Resources Information Center

Zhang, Aimao; Aasheim, Cheryl L.

2011-01-01

Numerous studies have identified causal factors for academic success. Factors vary from personal factors, such as cognitive style (McKenzie & Schweitzer, 2001), to social factors, such as culture differences (Aysan, Tanriogen, & Tanriogen, 1996). However, in these studies it is re-searchers who theorized the causal dimensions and…

Annual research review: Rare genotypes and childhood psychopathology--uncovering diverse developmental mechanisms of ADHD risk.

PubMed

Scerif, Gaia; Baker, Kate

2015-03-01

Through the increased availability and sophistication of genetic testing, it is now possible to identify causal diagnoses in a growing proportion of children with neurodevelopmental disorders. In addition to developmental delay and intellectual disability, many genetic disorders are associated with high risks of psychopathology, which curtail the wellbeing of affected individuals and their families. Beyond the identification of significant clinical needs, understanding the diverse pathways from rare genetic mutations to cognitive dysfunction and emotional-behavioural disturbance has theoretical and practical utility. We overview (based on a strategic search of the literature) the state-of-the-art on causal mechanisms leading to one of the most common childhood behavioural diagnoses - attention deficit hyperactivity disorder (ADHD) - in the context of specific genetic disorders. We focus on new insights emerging from the mapping of causal pathways from identified genetic differences to neuronal biology, brain abnormalities, cognitive processing differences and ultimately behavioural symptoms of ADHD. First, ADHD research in the context of rare genotypes highlights the complexity of multilevel mechanisms contributing to psychopathology risk. Second, comparisons between genetic disorders associated with similar psychopathology risks can elucidate convergent or distinct mechanisms at each level of analysis, which may inform therapeutic interventions and prognosis. Third, genetic disorders provide an unparalleled opportunity to observe dynamic developmental interactions between neurocognitive risk and behavioural symptoms. Fourth, variation in expression of psychopathology risk within each genetic disorder points to putative moderating and protective factors within the genome and the environment. A common imperative emerging within psychopathology research is the need to investigate mechanistically how developmental trajectories converge or diverge between and within genotype-defined groups. Crucially, as genetic predispositions modify interaction dynamics from the outset, longitudinal research is required to understand the multi-level developmental processes that mediate symptom evolution. © 2014 Association for Child and Adolescent Mental Health.

DES daughters in France: experts' points of view on the various genital, uterine and obstetric pathologies, and in utero DES exposure.

PubMed

Clement, R; Guilbaud, E; Barrios, L; Rougé-Maillart, C; Jousset, N; Rodat, O

2014-10-01

Compensation of diethylstilbestrol exposure depends on the judicial system. In France, girls having been exposed to diethylstilbestrol are currently being compensated, and each exposure victim is being evaluated. Fifty-nine expert evaluations were studied to determine the causal relation between exposure to diethylstilbestrol and the pathologies attributable to diethylstilbestrol. The following were taken into consideration: age at the first signs of the pathology; age of the sufferer at the time of evaluation; the pathologies grouped into five categories: fertility disorders - cancers - mishaps during pregnancy - psychosomatic complaints - pathologies of "3rd generation DES victims"; submission of proof of DES exposure; the degree of causality determined (direct, indirect, ruled out). 61% of the cases related to fertility disorders, 28.8% to cancer pathologies (clear-cell adenocarcinoma), 18.6% to mishaps during pregnancy, 8.5% to disorders resulting from preterm delivery, and 3.4% to psychosomatic disorders. Some cases involved a combination of two types of complaints. Indirect causality was determined in 47.1% of the cases involving primary sterility, in 66.7% involving secondary sterility, and in 5 out of 6 cases of total sterility. There is direct causality between in utero diethylstilbestrol exposure and vaginal or cervical clear cell adenocarcinoma. Causality is indirect in the case of disorders linked to prematurity in third generation victims. Causality was determined by the experts on the basis of scientific criteria which attribute the presenting pathologies to diethylstilbestrol exposure. When other risk factors come into play, or when exposure is indirect (third generation), this causality is diminished. © IMechE 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Mapping Risks of Indonesian Tuna Supply Chain

NASA Astrophysics Data System (ADS)

Karningsih, P. D.; Anggrahini, D.; Kurniati, N.; Suef, M.; Fachrur, A. R.; Syahroni, N.

2018-04-01

Due to its high economic value and is produced by many countries, Tuna is considered as one of the world’s popular fish. Demand for Tuna species are very high and it usually sells in three form: fresh, frozen or canned. Competition in Tuna trading is challengin with the potential risk of price and supply fluctuations. With recent focus of Indonesia government that see the future of Indonesia civilization depend on the oceans and as the three biggest Tuna producing country, Ministry of Marine Affairs and Fisheries should ensure sustainability and competitiveness of Indonesian tuna. Therefore, there is a great need to develop a proper and effective strategy to manage potential risks in Indonesian Tuna supply chain. This paper is aimed at identifying and mapping potential Tuna supply chain risks and its interrelationships that would assist government in determining proper strategies to manage Indonesian Tuna. A framework for identifying Tuna supply chain risks is proposed. Generic risk structure of Supply Chain Risk Identification System is adopted and modified to match with particular object, which is Indonesian Tuna. The proposed model consists of hierarchical and causal structure that encompass potential risks of Tuna supply chain operations from fishing, trading, processing and distribution. The causal structure consist of risk events and its risk agents which is the cause of risk events. To ensure the root cause of risk events are identified properly, five why’s analysis is utilized to obtain risk agents. This proposed model also captures risk interrelationship between internal and external environment of Tuna supply chain. Preliminary result of this study identifies 15 risk events and 13 risk factors on fishing and trading operations and maps their interrelationships.

Meat and colo-rectal cancer.

PubMed

Hill, M J

1999-05-01

In early epidemiological studies of diet and cancer the stress was on the search for causal factors. Population (ecological) studies tended to show a strong correlation between meat intake, particularly red meat, and the risk of colo-rectal cancer. They also tended to show meat to be strongly inversely correlated with cancers of the stomach and oesophagus and liver. Early case-control studies tended to support the postulated role for red meat in colo-rectal carcinogenesis, although more recent case-control studies, particularly those from Europe, have tended to show no relationship. The cohort studies in general failed to detect any relationship between meat intake and colo-rectal cancer risk. The available evidence points to the intake of protective factors such as vegetables and whole-grain cereals being the main determinants of colo-rectal cancer risk, with meat intake only coincidentally related.

Research on injury compensation and health outcomes: ignoring the problem of reverse causality led to a biased conclusion.

PubMed

Spearing, Natalie M; Connelly, Luke B; Nghiem, Hong S; Pobereskin, Louis

2012-11-01

This study highlights the serious consequences of ignoring reverse causality bias in studies on compensation-related factors and health outcomes and demonstrates a technique for resolving this problem of observational data. Data from an English longitudinal study on factors, including claims for compensation, associated with recovery from neck pain (whiplash) after rear-end collisions are used to demonstrate the potential for reverse causality bias. Although it is commonly believed that claiming compensation leads to worse recovery, it is also possible that poor recovery may lead to compensation claims--a point that is seldom considered and never addressed empirically. This pedagogical study compares the association between compensation claiming and recovery when reverse causality bias is ignored and when it is addressed, controlling for the same observable factors. When reverse causality is ignored, claimants appear to have a worse recovery than nonclaimants; however, when reverse causality bias is addressed, claiming compensation appears to have a beneficial effect on recovery, ceteris paribus. To avert biased policy and judicial decisions that might inadvertently disadvantage people with compensable injuries, there is an urgent need for researchers to address reverse causality bias in studies on compensation-related factors and health. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of a functional enhancer variant within the chronic pancreatitis-associated SPINK1 c.101A>G (p.Asn34Ser)-containing haplotype.

PubMed

Boulling, Arnaud; Masson, Emmanuelle; Zou, Wen-Bin; Paliwal, Sumit; Wu, Hao; Issarapu, Prachand; Bhaskar, Seema; Génin, Emmanuelle; Cooper, David N; Li, Zhao-Shen; Chandak, Giriraj R; Liao, Zhuan; Chen, Jian-Min; Férec, Claude

2017-08-01

The haplotype harboring the SPINK1 c.101A>G (p.Asn34Ser) variant (also known as rs17107315:T>C) represents the most important heritable risk factor for idiopathic chronic pancreatitis identified to date. The causal variant contained within this risk haplotype has however remained stubbornly elusive. Herein, we set out to resolve this enigma by employing a hypothesis-driven approach. First, we searched for variants in strong linkage disequilibrium (LD) with rs17107315:T>C using HaploReg v4.1. Second, we identified two candidate SNPs by visual inspection of sequences spanning all 25 SNPs found to be in LD with rs17107315:T>C, guided by prior knowledge of pancreas-specific transcription factors and their cognate binding sites. Third, employing a novel cis-regulatory module (CRM)-guided approach to further filter the two candidate SNPs yielded a solitary candidate causal variant. Finally, combining data from phylogenetic conservation and chromatin accessibility, cotransfection transactivation experiments, and population genetic studies, we suggest that rs142703147:C>A, which disrupts a PTF1L-binding site within an evolutionarily conserved HNF1A-PTF1L CRM located ∼4 kb upstream of the SPINK1 promoter, contributes to the aforementioned chronic pancreatitis risk haplotype. Further studies are required not only to improve the characterization of this functional SNP but also to identify other functional components that might contribute to this high-risk haplotype. © 2017 Wiley Periodicals, Inc.

Adolescent Victimization and Early-Adult Psychopathology: Approaching Causal Inference Using a Longitudinal Twin Study to Rule Out Noncausal Explanations

PubMed Central

Schaefer, Jonathan D.; Moffitt, Terrie E.; Arseneault, Louise; Danese, Andrea; Fisher, Helen L.; Houts, Renate; Sheridan, Margaret A.; Wertz, Jasmin; Caspi, Avshalom

2017-01-01

Adolescence is the peak age for both victimization and mental disorder onset. Previous research has reported associations between victimization exposure and many psychiatric conditions. However, causality remains controversial. Within the Environmental Risk Longitudinal Twin Study, we tested whether seven types of adolescent victimization increased risk of multiple psychiatric conditions and approached causal inference by systematically ruling out noncausal explanations. Longitudinal within-individual analyses showed that victimization was followed by increased mental health problems over a childhood baseline of emotional/behavioral problems. Discordant-twin analyses showed that victimization increased risk of mental health problems independent of family background and genetic risk. Both childhood and adolescent victimization made unique contributions to risk. Victimization predicted heightened generalized liability (the “p factor”) to multiple psychiatric spectra, including internalizing, externalizing, and thought disorders. Results recommend violence reduction and identification and treatment of adolescent victims to reduce psychiatric burden. PMID:29805917

Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction.

PubMed

Jørgensen, Anders Berg; Frikke-Schmidt, Ruth; West, Anders Sode; Grande, Peer; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

2013-06-01

Elevated non-fasting triglycerides mark elevated levels of remnant cholesterol. Using a Mendelian randomization approach, we tested whether genetically increased remnant cholesterol in hypertriglyceridaemia due to genetic variation in the apolipoprotein A5 gene (APOA5) associates with an increased risk of myocardial infarction (MI). We resequenced the core promoter and coding regions of APOA5 in individuals with the lowest 1% (n = 95) and highest 2% (n = 190) triglyceride levels in the Copenhagen City Heart Study (CCHS, n = 10 391). Genetic variants which differed in frequency between the two extreme triglyceride groups (c.-1131T > C, S19W, and c.*31C > T; P-value: 0.06 to <0.001), thus suggesting an effect on triglyceride levels, were genotyped in the Copenhagen General Population Study (CGPS), the CCHS, and the Copenhagen Ischemic Heart Disease Study (CIHDS), comprising a total of 5705 MI cases and 54 408 controls. Genotype combinations of these common variants associated with increases in non-fasting triglycerides and calculated remnant cholesterol of, respectively, up to 68% (1.10 mmol/L) and 56% (0.40 mmol/L) (P < 0.001), and with a corresponding odds ratio for MI of 1.87 (95% confidence interval: 1.25-2.81). Using APOA5 genotypes in instrumental variable analysis, the observational hazard ratio for a doubling in non-fasting triglycerides was 1.57 (1.32-2.68) compared with a causal genetic odds ratio of 1.94 (1.40-1.85) (P for comparison = 0.28). For calculated remnant cholesterol, the corresponding values were 1.67(1.38-2.02) observational and 2.23(1.48-3.35) causal (P for comparison = 0.21). These data are consistent with a causal association between elevated levels of remnant cholesterol in hypertriglyceridaemia and an increased risk of MI. Limitations include that remnants were not measured directly, and that APOA5 genetic variants may influence other lipoprotein parameters.

Should visceral fat be reduced to increase longevity?

PubMed

Finelli, Carmine; Sommella, Luigi; Gioia, Saverio; La Sala, Nicolina; Tarantino, Giovanni

2013-09-01

Several epidemiologic studies have implicated visceral fat as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and death. Utilizing novel models of visceral obesity, numerous studies have demonstrated that the relationship between visceral fat and longevity is causal while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. Specific recommended intake levels vary based on a number of factors, including current weight, activity levels, and weight loss goals. It is discussed the need of reducing the visceral fat as a potential treatment strategy to prevent or delay age-related diseases and to increase longevity. Copyright © 2013 Elsevier B.V. All rights reserved.

[Causality link in criminal law: role of epidemiology].

PubMed

Zocchetti, C; Riboldi, L

2003-01-01

This paper focusses on the role of epidemiology in demonstrating causality in criminal trials of toxic tort litigation. First of all, consideration is given of the specificity of the criminal trial and of the role of the epidemiologist as expert witness. As a second step the concept of causality is examined separating general from specific (individual level) causality. As regards general causality, strategies based on some criteria (example: Bradford-Hill criteria) are contrasted with approaches that do not consider causality a matter of science but one of health policy; and specific methods frequently used (meta-analysis, risk assessment, International Boards evaluation,....) are discussed, with special reference to the adoption of high-level standards and to the context of cross-examination. As regards individual level causality the difficulties of the epidemiologic approach to such evaluation are stressed, with special reference to topics like expected value, attributable risk, and probability of causation. All examples are taken from Italian court trials. A general comment on the difficulties of using the criminal trial (dominated by the "but for" rule) for toxic tort litigation and on the opportunity to switch to trials (civil, administrative) with less stringent causal rules ("more probable than not") is offered, with a consideration also of what are called "class actions".

Intracranial Pressure and Its Relationship to Glaucoma: Current Understanding and Future Directions

PubMed Central

ROY CHOWDHURY, Uttio; FAUTSCH, Michael P.

2015-01-01

Retrospective and prospective studies looking at the role of cerebrospinal fluid pressure (CSFP)/intracranial pressure (ICP) have stimulated new theories and hypotheses regarding the underlying causal events for glaucoma. Most recently, studies supporting a low CSFP/ICP as a risk factor for glaucoma have been published. This review summarizes the current understanding of CSFP/ICP and its potential role in the pathogenicity of the disease. PMID:27350948

Toward a cumulative ecological risk model for the etiology of child maltreatment

PubMed Central

MacKenzie, Michael J.; Kotch, Jonathan B.; Lee, Li-Ching

2011-01-01

The purpose of the current study was to further the integration of cumulative risk models with empirical research on the etiology of child maltreatment. Despite the well-established literature supporting the importance of the accumulation of ecological risk, this perspective has had difficulty infiltrating empirical maltreatment research and its tendency to focus on more limited risk factors. Utilizing a sample of 842 mother-infant dyads, we compared the capacity of individual risk factors and a cumulative index to predict maltreatment reports in a prospective longitudinal investigation over the first sixteen years of life. The total load of risk in early infancy was found to be related to maternal cognitions surrounding her new role, measures of social support and well-being, and indicators of child cognitive functioning. After controlling for total level of cumulative risk, most single factors failed to predict later maltreatment reports and no single variable provided odd-ratios as powerful as the predictive power of a cumulative index. Continuing the shift away from simplistic causal models toward an appreciation for the cumulative nature of risk would be an important step forward in the way we conceptualize intervention and support programs, concentrating them squarely on alleviating the substantial risk facing so many of society’s families. PMID:24817777

Update on Multiple Ovulations in Dairy Cattle

PubMed Central

Macmillan, Kira; Kastelic, John P.

2018-01-01

Simple Summary Multiple ovulations (MOV) in cattle can lead to twin pregnancies, which negatively affects the health, production, and reproduction of cows. Despite many studies, the causal mechanisms behind MOV are still not well understood. There is a general agreement that MOV are more likely during periods of low progesterone (P4), which may increase the luteinizing hormone (LH) release at the time of selection, resulting in more than one follicle becoming dominant. The MOV rate also increases in older cows and when the selection of a dominant follicle occurs concurrently with a high milk yield. Additional risk factors for MOV are ovarian cysts, diet, season, and genetics. A better understanding of the mechanisms underlying MOV may help to mitigate twinning, perhaps through the appropriate reproductive management protocols or genetic selection. Abstract This review updates the causal mechanisms and risk factors for multiple ovulations (MOV) in cattle. Clearly, MOV can lead to twin pregnancies, which negatively affects the health, production, and reproduction of cows. Therefore, a better understanding of the factors causing MOV may help to reduce twinning. Multiple ovulations occur after two or more follicles deviate and achieve codominance. The MOV rate is influenced by a complex network of hormones. For example, MOV is more common during periods of low progesterone (P4), that is, in anovulatory cattle or when luteolysis coincides with the selection of the future ovulatory follicle. There is also strong evidence for the luteinizing hormone (LH) being the primary factor leading to codominance, as high P4 concentrations suppress the transient LH surges and can reduce the ovulation rate in cattle or even inhibit deviation. Rates of MOV are increased in older and higher-producing dairy cows. Increased milk production and dry matter intake (DMI) increases hormone clearance, including P4; however, the association between milk yield and MOV has not been consistent. Additional risk factors for MOV include ovarian cysts, diet, season, and genetics. PMID:29695075

Alcohol intake and the risk of intracerebral hemorrhage in the elderly: The MUCH-Italy.

PubMed

Costa, Paolo; Grassi, Mario; Iacoviello, Licia; Zedde, Marialuisa; Marcheselli, Simona; Silvestrelli, Giorgio; DeLodovici, Maria Luisa; Sessa, Maria; Zini, Andrea; Paciaroni, Maurizio; Azzini, Cristiano; Gamba, Massimo; Del Sette, Massimo; Toriello, Antonella; Gandolfo, Carlo; Bonifati, Domenico Marco; Tassi, Rossana; Cavallini, Anna; Chiti, Alberto; Calabrò, Rocco Salvatore; Grillo, Francesco; Bovi, Paolo; Tomelleri, Giampaolo; Di Castelnuovo, Augusto; Ritelli, Marco; Agnelli, Giancarlo; De Vito, Alessandro; Pugliese, Nicola; Martini, Giuseppe; Lodigiani, Corrado; Morotti, Andrea; Poli, Loris; De Giuli, Valeria; Caria, Filomena; Cornali, Claudio; de Gaetano, Giovanni; Colombi, Marina; Padovani, Alessandro; Pezzini, Alessandro

2018-06-13

To investigate the role of alcohol as a causal factor for intracerebral hemorrhage (ICH) and whether its effects might vary according to the pathogenic mechanisms underlying cerebral bleeding. We performed a case-control analysis, comparing a cohort of consecutive white patients with ICH aged 55 years and older with a group of age- and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) between 2002 and 2014. Participants were dichotomized into excessive drinkers (>45 g of alcohol) and light to moderate drinkers or nondrinkers. To isolate the unconfounded effect of alcohol on ICH, we used causal directed acyclic graphs and the back-door criterion to select a minimal sufficient adjustment set(s) of variables for multivariable analyses. Analyses were performed on the whole group as well as separately for lobar and deep ICH. We analyzed 3,173 patients (1,471 lobar ICH and 1,702 deep ICH) and 3,155 controls. After adjusting for the preselected variables in the minimal sufficient adjustments, heavy alcohol intake was associated with deep ICH risk (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.36-2.09) as well as with the overall risk of ICH (OR, 1.38; 95% CI, 1.17-1.63), whereas no effect was found for lobar ICH (OR, 1.01; 95% CI, 0.77-1.32). In white people aged 55 years and older, high alcohol intake might exert a causal effect on ICH, with a prominent role in the vascular pathologies underlying deep ICH. © 2018 American Academy of Neurology.

DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia.

PubMed

Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

2016-04-01

5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple 'hits' are required for disease progression; an initial genetic abnormality followed by additional secondary 'hits'. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development.

Epidemiology of Foot and Mouth Disease in Ethiopia: a Retrospective Analysis of District Level Outbreaks, 2007-2012.

PubMed

Jemberu, W T; Mourits, M C M; Sahle, M; Siraw, B; Vernooij, J C M; Hogeveen, H

2016-12-01

This study aimed at determining the incidence, distribution, risk factors, and causal serotypes of foot and mouth disease (FMD) outbreaks in Ethiopia based on 5 years of retrospective outbreak data (September 2007 until August 2012). District level outbreak data were collected from 115 randomly selected districts using a questionnaire administered to district animal health officers. The national incidence of FMD outbreaks during the study period was 1.45 outbreaks per five district years. Outbreaks were geographically widespread affecting all major regional states in the country and were more frequent in the central, southern, and southeastern parts of the country. Neither long-term nor seasonal trends were observed in the incidence of outbreaks. A mixed effects logistic regression analysis revealed that the type of production system (market oriented system versus subsistence systems), presence of a major livestock market and/or route, and adjacency to a national parks or wildlife sanctuary were found to be associated with increased risk of outbreaks in the districts. FMD virus serotypes O, A, SAT 2, and SAT 1 were identified as the causal serotypes of the outbreaks during the study period. Whereas O was the dominant serotype, SAT 2 was the serotype that showed increase in relative frequency of occurrence. The estimated incidence of outbreaks is useful in assessing the economic impacts of the disease, and the identified risk factors provide important knowledge to target a progressive FMD control policy for Ethiopia. © 2015 Blackwell Verlag GmbH.

Do causal concentration-response functions exist? A critical review of associational and causal relations between fine particulate matter and mortality.

PubMed

Cox, Louis Anthony Tony

2017-08-01

Concentration-response (C-R) functions relating concentrations of pollutants in ambient air to mortality risks or other adverse health effects provide the basis for many public health risk assessments, benefits estimates for clean air regulations, and recommendations for revisions to existing air quality standards. The assumption that C-R functions relating levels of exposure and levels of response estimated from historical data usefully predict how future changes in concentrations would change risks has seldom been carefully tested. This paper critically reviews literature on C-R functions for fine particulate matter (PM2.5) and mortality risks. We find that most of them describe historical associations rather than valid causal models for predicting effects of interventions that change concentrations. The few papers that explicitly attempt to model causality rely on unverified modeling assumptions, casting doubt on their predictions about effects of interventions. A large literature on modern causal inference algorithms for observational data has been little used in C-R modeling. Applying these methods to publicly available data from Boston and the South Coast Air Quality Management District around Los Angeles shows that C-R functions estimated for one do not hold for the other. Changes in month-specific PM2.5 concentrations from one year to the next do not help to predict corresponding changes in average elderly mortality rates in either location. Thus, the assumption that estimated C-R relations predict effects of pollution-reducing interventions may not be true. Better causal modeling methods are needed to better predict how reducing air pollution would affect public health.

Genetic risk factors for ovarian cancer and their role for endometriosis risk.

PubMed

Burghaus, Stefanie; Fasching, Peter A; Häberle, Lothar; Rübner, Matthias; Büchner, Kathrin; Blum, Simon; Engel, Anne; Ekici, Arif B; Hartmann, Arndt; Hein, Alexander; Beckmann, Matthias W; Renner, Stefan P

2017-04-01

Several genetic variants have been validated as risk factors for ovarian cancer. Endometriosis has also been described as a risk factor for ovarian cancer. Identifying genetic risk factors that are common to the two diseases might help improve our understanding of the molecular pathogenesis potentially linking the two conditions. In a hospital-based case-control analysis, 12 single nucleotide polymorphisms (SNPs), validated by the Ovarian Cancer Association Consortium (OCAC) and the Collaborative Oncological Gene-environment Study (COGS) project, were genotyped using TaqMan® OpenArray™ analysis. The cases consisted of patients with endometriosis, and the controls were healthy individuals without endometriosis. A total of 385 cases and 484 controls were analyzed. Odds ratios and P values were obtained using simple logistic regression models, as well as from multiple logistic regression models with adjustment for clinical predictors. rs11651755 in HNF1B was found to be associated with endometriosis in this case-control study. The OR was 0.66 (95% CI, 0.51 to 0.84) and the P value after correction for multiple testing was 0.01. None of the other genotypes was associated with a risk for endometriosis. As rs11651755 in HNF1B modified both the ovarian cancer risk and also the risk for endometriosis, HNF1B may be causally involved in the pathogenetic pathway leading from endometriosis to ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic Influences on Conduct Disorder

PubMed Central

Salvatore, Jessica E.; Dick, Danielle M.

2016-01-01

Conduct disorder (CD) is a moderately heritable psychiatric disorder of childhood and adolescence characterized by aggression toward people and animals, destruction of property, deceitfulness or theft, and serious violation of rules. Genome-wide scans using linkage and association methods have identified a number of suggestive genomic regions that are pending replication. A small number of candidate genes (e.g., GABRA2, MAOA, SLC6A4, AVPR1A) are associated with CD related phenotypes across independent studies; however, failures to replicate also exist. Studies of gene-environment interplay show that CD genetic predispositions also contribute to selection into higher-risk environments, and that environmental factors can alter the importance of CD genetic factors and differentially methylate CD candidate genes. The field’s understanding of CD etiology will benefit from larger, adequately powered studies in gene identification efforts; the incorporation of polygenic approaches in gene-environment interplay studies; attention to the mechanisms of risk from genes to brain to behavior; and the use of genetically informative data to test quasi-causal hypotheses about purported risk factors. PMID:27350097

Bayesian Networks Improve Causal Environmental Assessments for Evidence-Based Policy.

PubMed

Carriger, John F; Barron, Mace G; Newman, Michael C

2016-12-20

Rule-based weight of evidence approaches to ecological risk assessment may not account for uncertainties and generally lack probabilistic integration of lines of evidence. Bayesian networks allow causal inferences to be made from evidence by including causal knowledge about the problem, using this knowledge with probabilistic calculus to combine multiple lines of evidence, and minimizing biases in predicting or diagnosing causal relationships. Too often, sources of uncertainty in conventional weight of evidence approaches are ignored that can be accounted for with Bayesian networks. Specifying and propagating uncertainties improve the ability of models to incorporate strength of the evidence in the risk management phase of an assessment. Probabilistic inference from a Bayesian network allows evaluation of changes in uncertainty for variables from the evidence. The network structure and probabilistic framework of a Bayesian approach provide advantages over qualitative approaches in weight of evidence for capturing the impacts of multiple sources of quantifiable uncertainty on predictions of ecological risk. Bayesian networks can facilitate the development of evidence-based policy under conditions of uncertainty by incorporating analytical inaccuracies or the implications of imperfect information, structuring and communicating causal issues through qualitative directed graph formulations, and quantitatively comparing the causal power of multiple stressors on valued ecological resources. These aspects are demonstrated through hypothetical problem scenarios that explore some major benefits of using Bayesian networks for reasoning and making inferences in evidence-based policy.

Linking parent perceptions of children's weight to early coronary risk factors: results from the CARDIAC Project.

PubMed

Stabler, M E; Cottrell, L; Lilly, C

2014-01-01

Obesity is a public health threat because of the increasing prevalence in childhood and its causal relationship to the leading cause of death in America, heart disease. Detecting early signs of cardiovascular disease (CVD) risk factors in children and appropriately intervening to reverse the unhealthy trajectory associated with childhood obesity is of great importance. The objective of this study is to observe parental perception of their child's body mass index (BMI) and find associations between inaccurately estimated children and CVD risk factors. This study analyzed the association between 147 rural fifth grade students' lipid profiles and parents' self-reported survey who participated in the 2008-2011 Coronary Artery Risk Detection in Appalachian Communities study. After controlling for covariates, underestimated children were more likely to have higher log-transformed triglyceride and systolic blood pressure values and overestimated children were more likely to have lower systolic blood pressure. Underestimating a child's BMI is associated with coronary risk-related factors, while overestimating a child's BMI is associate with a protective CVD marker. A follow-up study examining the development of CVD risk factors in children of parents who inaccurately estimate their BMI would help clarify this relationship. Knowledge of how parental perceptions directly influence higher lipid levels in children could have an impact on public health efforts in the fight against childhood obesity in rural environments.

The influence of linguistic and cognitive factors on the time course of verb-based implicit causality.

PubMed

Koornneef, Arnout; Dotlačil, Jakub; van den Broek, Paul; Sanders, Ted

2016-01-01

In three eye-tracking experiments the influence of the Dutch causal connective "want" (because) and the working memory capacity of readers on the usage of verb-based implicit causality was examined. Experiments 1 and 2 showed that although a causal connective is not required to activate implicit causality information during reading, effects of implicit causality surfaced more rapidly and were more pronounced when a connective was present in the discourse than when it was absent. In addition, Experiment 3 revealed that-in contrast to previous claims-the activation of implicit causality is not a resource-consuming mental operation. Moreover, readers with higher and lower working memory capacities behaved differently in a dual-task situation. Higher span readers were more likely to use implicit causality when they had all their working memory resources at their disposal. Lower span readers showed the opposite pattern as they were more likely to use the implicit causality cue in the case of an additional working memory load. The results emphasize that both linguistic and cognitive factors mediate the impact of implicit causality on text comprehension. The implications of these results are discussed in terms of the ongoing controversies in the literature-that is, the focusing-integration debate and the debates on the source of implicit causality.

Myalgic encephalomyelitis, chronic fatigue syndrome: An infectious disease.

PubMed

Underhill, R A

2015-12-01

The etiology of myalgic encephalomyelitis also known as chronic fatigue syndrome or ME/CFS has not been established. Controversies exist over whether it is an organic disease or a psychological disorder and even the existence of ME/CFS as a disease entity is sometimes denied. Suggested causal hypotheses have included psychosomatic disorders, infectious agents, immune dysfunctions, autoimmunity, metabolic disturbances, toxins and inherited genetic factors. Clinical, immunological and epidemiological evidence supports the hypothesis that: ME/CFS is an infectious disease; the causal pathogen persists in patients; the pathogen can be transmitted by casual contact; host factors determine susceptibility to the illness; and there is a population of healthy carriers, who may be able to shed the pathogen. ME/CFS is endemic globally as sporadic cases and occasional cluster outbreaks (epidemics). Cluster outbreaks imply an infectious agent. An abrupt flu-like onset resembling an infectious illness occurs in outbreak patients and many sporadic patients. Immune responses in sporadic patients resemble immune responses in other infectious diseases. Contagion is shown by finding secondary cases in outbreaks, and suggested by a higher prevalence of ME/CFS in sporadic patients' genetically unrelated close contacts (spouses/partners) than the community. Abortive cases, sub-clinical cases, and carrier state individuals were found in outbreaks. The chronic phase of ME/CFS does not appear to be particularly infective. Some healthy patient-contacts show immune responses similar to patients' immune responses, suggesting exposure to the same antigen (a pathogen). The chronicity of symptoms and of immune system changes and the occurrence of secondary cases suggest persistence of a causal pathogen. Risk factors which predispose to developing ME/CFS are: a close family member with ME/CFS; inherited genetic factors; female gender; age; rest/activity; previous exposure to stress or toxins; various infectious diseases preceding the onset of ME/CFS; and occupational exposure of health care professionals. The hypothesis implies that ME/CFS patients should not donate blood or tissue and usual precautions should be taken when handling patients' blood and tissue. No known pathogen has been shown to cause ME/CFS. Confirmation of the hypothesis requires identification of a causal pathogen. Research should focus on a search for unknown and known pathogens. Finding a causal pathogen could assist with diagnosis; help find a biomarker; enable the development of anti-microbial treatments; suggest preventive measures; explain pathophysiological findings; and reassure patients about the validity of their symptoms.

Effects of the Ambient Fine Particulate Matter on Public Awareness of Lung Cancer Risk in China: Evidence from the Internet-Based Big Data Platform

PubMed Central

Zhang, Xinyu; Hou, Jie

2017-01-01

Background In October 2013, the International Agency for Research on Cancer classified the particulate matter from outdoor air pollution as a group 1 carcinogen and declared that particulate matter can cause lung cancer. Fine particular matter (PM2.5) pollution is becoming a serious public health concern in urban areas of China. It is essential to emphasize the importance of the public’s awareness and knowledge of modifiable risk factors of lung cancer for prevention. Objective The objective of our study was to explore the public’s awareness of the association of PM2.5 with lung cancer risk in China by analyzing the relationship between the daily PM2.5 concentration and searches for the term “lung cancer” on an Internet big data platform, Baidu. Methods We collected daily PM2.5 concentration data and daily Baidu Index data in 31 Chinese capital cities from January 1, 2014 to December 31, 2016. We used Spearman correlation analysis to explore correlations between the daily Baidu Index for lung cancer searches and the daily average PM2.5 concentration. Granger causality test was used to analyze the causal relationship between the 2 time-series variables. Results In 23 of the 31 cities, the pairwise correlation coefficients (Spearman rho) between the daily Baidu Index for lung cancer searches and the daily average PM2.5 concentration were positive and statistically significant (P<.05). However, the correlation between the daily Baidu Index for lung cancer searches and the daily average PM2.5 concentration was poor (all r2s<.1). Results of Granger causality testing illustrated that there was no unidirectional causality from the daily PM2.5 concentration to the daily Baidu Index for lung cancer searches, which was statistically significant at the 5% level for each city. Conclusions The daily average PM2.5 concentration had a weak positive impact on the daily search interest for lung cancer on the Baidu search engine. Well-designed awareness campaigns are needed to enhance the general public’s awareness of the association of PM2.5 with lung cancer risk, to lead the public to seek more information about PM2.5 and its hazards, and to cope with their environment and its risks appropriately. PMID:28974484

Risk and protective factors for childhood asthma: what is the evidence?

PubMed Central

Castro-Rodriguez, Jose A.; Forno, Erick; Rodriguez-Martinez, Carlos E.; Celedón, Juan C.

2016-01-01

In order to summarize the principal findings on risk and protective factors for childhood asthma, we retrieved systematic reviews on these topics in children (ages 1 to 18 years), up to January 2016, through MEDLINE, EMBASE, CINAHL, SCOPUS and CDSR. Two hundred twenty seven studies were searched from databases. Among those, 41 systematic reviews (SRs) were included: 9 focused on prenatal factors, 5 on perinatal factors, and 27 on postnatal factors. Of these 41 SRs, 83% had good methodological quality, as determined by the AMSTAR tool. After reviewing all evidence, parental asthma, prenatal environmental tobacco smoke and prematurity (particularly very preterm birth) are well-established risk factors for childhood asthma. Current findings do suggest mild to moderate causal effects of certain modifiable behaviors or exposures during pregnancy (maternal weight gain or obesity, maternal use of antibiotics or paracetamol, and maternal stress), the perinatal period (birth by Caesarean delivery), or postnatal life (severe RSV infection, overweight or obesity, indoor exposure to mold or fungi, and outdoor air pollution) on childhood asthma, but this suggestive evidence must be confirmed in interventional studies or (if interventions are not feasible) well-designed prospective studies. PMID:27286779

How Can Historical Understanding Best be Assessed? Use of Prediction Tasks To Assess How Students Understand the Role of Causal Factors that Produce Historical Events.

ERIC Educational Resources Information Center

Alonso-Tapia, Jesus; Villa, Jose Luis

1999-01-01

Examines the viability of using hypothetical problems that need the application of causal models for their solution as a method to assessing understanding in the social sciences. Explains that this method was used to describe how seventh-grade students understand causal factors affecting the "discovery and colonization of America." (CMK)

The causal role of smoking on the risk of hip or knee replacement due to primary osteoarthritis: a Mendelian randomisation analysis of the HUNT study.

PubMed

Johnsen, M B; Vie, G Å; Winsvold, B S; Bjørngaard, J H; Åsvold, B O; Gabrielsen, M E; Pedersen, L M; Hellevik, A I; Langhammer, A; Furnes, O; Flugsrud, G B; Skorpen, F; Romundstad, P R; Storheim, K; Nordsletten, L; Zwart, J A

2017-06-01

Smoking has been associated with a reduced risk of hip and knee osteoarthritis (OA) and subsequent joint replacement. The aim of the present study was to assess whether the observed association is likely to be causal. 55,745 participants of a population-based cohort were genotyped for the rs1051730 C > T single-nucleotide polymorphism (SNP), a proxy for smoking quantity among smokers. A Mendelian randomization analysis was performed using rs1051730 as an instrument to evaluate the causal role of smoking on the risk of hip or knee replacement (combined as total joint replacement (TJR)). Association between rs1051730 T alleles and TJR was estimated by hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were adjusted for age and sex. Smoking quantity (no. of cigarettes) was inversely associated with TJR (HR 0.97, 95% CI 0.97-0.98). In the Mendelian randomization analysis, rs1051730 T alleles were associated with reduced risk of TJR among current smokers (HR 0.84, 95% CI 0.76-0.98, per T allele), however we found no evidence of association among former (HR 0.97, 95% CI 0.88-1.07) and never smokers (HR 0.97, 95% CI 0.89-1.06). Neither adjusting for body mass index (BMI), cardiovascular disease (CVD) nor accounting for the competing risk of mortality substantially changed the results. This study suggests that smoking may be causally associated with the reduced risk of TJR. Our findings add support to the inverse association found in previous observational studies. More research is needed to further elucidate the underlying mechanisms of this causal association. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Risk factors for Raynaud's phenomenon among workers in poultry slaughterhouses and canning factories.

PubMed

Kaminski, M; Bourgine, M; Zins, M; Touranchet, A; Verger, C

1997-04-01

Apart from the use of vibrating tools, little is known about risk factors for Raynaud's phenomenon. However, it has been hypothesized that this disorder may have a multifactorial aetiology, involving potential causal or triggering factors which can be found in the workplace. The objective of the study is to identify individual and occupational risk factors of Raynaud's phenomenon in a population of workers not exposed to vibration, but exposed to cold. The survey was carried out in 1987-1988 in 17 poultry slaughterhouses and six canning factories and included 1474 employees. Data were collected at the annual visit to the occupational health physician. Finger sensitivity to cold and Raynaud's phenomenon were identified from a list of symptoms occurring from exposure to cold. The role of potential risk factors was assessed using multiple logistic regression. A high prevalence of symptoms of finger sensitivity to cold was observed. Raynaud's phenomenon was more common in women than in men, was related to family history of the disease but not to smoking or alcohol consumption. After controlling for non-occupational factors, the following working conditions appeared as risk factors for Raynaud's phenomenon: use of plastic gloves, less than four rest breaks, breaks in an unheated place, continual repetition of the same series of operations, exertion of the arm or hand and being able to think of something else while working. The study showed that a number of working conditions were associated with an increased risk of Raynaud's phenomenon and finger sensitivity to cold. Changes in working conditions might reduce the risk of this disorder in the food processing industry.

Epidemiology of childhood conduct problems in Brazil: systematic review and meta-analysis.

PubMed

Murray, Joseph; Anselmi, Luciana; Gallo, Erika Alejandra Giraldo; Fleitlich-Bilyk, Bacy; Bordin, Isabel A

2013-10-01

This study aimed to review evidence on the prevalence of and risk factors for conduct problems in Brazil. We searched electronic databases and contacted Brazilian researchers up to 05/2012. Studies were included in the review if they reported the prevalence of or risk factors for conduct problems, conduct disorder, or oppositional defiant disorder for 100 + Brazilian children aged ≤18 years, systematically sampled in schools or the community. Prevalence rates and sex differences were meta-analysed. Risk factor studies were reviewed one by one. The average prevalence of conduct problems in screening questionnaires was 20.8%, and the average prevalence of conduct disorder/oppositional defiant disorder was 4.1%. There was systematic variation in the results of screening studies according to methodology: recruitment location, informants, instruments, impairment criterion for case definition, and response rates. Risk factors previously identified in high-income countries were mainly replicated in Brazil, including comorbid mental health problems, educational failure, low religiosity, harsh physical punishment and abuse, parental mental health problems, single parent family, and low socioeconomic status. However, boys did not always have higher risk for conduct problems than girls. Studies using screening questionnaires suggest that Brazilian children have higher rates of conduct problems than children in other countries, but diagnostic studies do not show this difference. Risk factors in Brazil were similar to those in high-income countries, apart from child sex. Future research should investigate developmental patterns of antisocial behaviour, employ a variety of research designs to identify causal risk mechanisms, and examine a broader range of risk factors.

Illness causal beliefs in Turkish immigrants

PubMed Central

Minas, Harry; Klimidis, Steven; Tuncer, Can

2007-01-01

Background People hold a wide variety of beliefs concerning the causes of illness. Such beliefs vary across cultures and, among immigrants, may be influenced by many factors, including level of acculturation, gender, level of education, and experience of illness and treatment. This study examines illness causal beliefs in Turkish-immigrants in Australia. Methods Causal beliefs about somatic and mental illness were examined in a sample of 444 members of the Turkish population of Melbourne. The socio-demographic characteristics of the sample were broadly similar to those of the Melbourne Turkish community. Five issues were examined: the structure of causal beliefs; the relative frequency of natural, supernatural and metaphysical beliefs; ascription of somatic, mental, or both somatic and mental conditions to the various causes; the correlations of belief types with socio-demographic, modernizing and acculturation variables; and the relationship between causal beliefs and current illness. Results Principal components analysis revealed two broad factors, accounting for 58 percent of the variation in scores on illness belief scales, distinctly interpretable as natural and supernatural beliefs. Second, beliefs in natural causes were more frequent than beliefs in supernatural causes. Third, some causal beliefs were commonly linked to both somatic and mental conditions while others were regarded as more specific to either somatic or mental disorders. Last, there was a range of correlations between endorsement of belief types and factors defining heterogeneity within the community, including with demographic factors, indicators of modernizing and acculturative processes, and the current presence of illness. Conclusion Results supported the classification of causal beliefs proposed by Murdock, Wilson & Frederick, with a division into natural and supernatural causes. While belief in natural causes is more common, belief in supernatural causes persists despite modernizing and acculturative influences. Different types of causal beliefs are held in relation to somatic or mental illness, and a variety of apparently logically incompatible beliefs may be concurrently held. Illness causal beliefs are dynamic and are related to demographic, modernizing, and acculturative factors, and to the current presence of illness. Any assumption of uniformity of illness causal beliefs within a community, even one that is relatively culturally homogeneous, is likely to be misleading. A better understanding of the diversity, and determinants, of illness causal beliefs can be of value in improving our understanding of illness experience, the clinical process, and in developing more effective health services and population health strategies. PMID:17645806

Illness causal beliefs in Turkish immigrants.

PubMed

Minas, Harry; Klimidis, Steven; Tuncer, Can

2007-07-24

People hold a wide variety of beliefs concerning the causes of illness. Such beliefs vary across cultures and, among immigrants, may be influenced by many factors, including level of acculturation, gender, level of education, and experience of illness and treatment. This study examines illness causal beliefs in Turkish-immigrants in Australia. Causal beliefs about somatic and mental illness were examined in a sample of 444 members of the Turkish population of Melbourne. The socio-demographic characteristics of the sample were broadly similar to those of the Melbourne Turkish community. Five issues were examined: the structure of causal beliefs; the relative frequency of natural, supernatural and metaphysical beliefs; ascription of somatic, mental, or both somatic and mental conditions to the various causes; the correlations of belief types with socio-demographic, modernizing and acculturation variables; and the relationship between causal beliefs and current illness. Principal components analysis revealed two broad factors, accounting for 58 percent of the variation in scores on illness belief scales, distinctly interpretable as natural and supernatural beliefs. Second, beliefs in natural causes were more frequent than beliefs in supernatural causes. Third, some causal beliefs were commonly linked to both somatic and mental conditions while others were regarded as more specific to either somatic or mental disorders. Last, there was a range of correlations between endorsement of belief types and factors defining heterogeneity within the community, including with demographic factors, indicators of modernizing and acculturative processes, and the current presence of illness. Results supported the classification of causal beliefs proposed by Murdock, Wilson & Frederick, with a division into natural and supernatural causes. While belief in natural causes is more common, belief in supernatural causes persists despite modernizing and acculturative influences. Different types of causal beliefs are held in relation to somatic or mental illness, and a variety of apparently logically incompatible beliefs may be concurrently held. Illness causal beliefs are dynamic and are related to demographic, modernizing, and acculturative factors, and to the current presence of illness. Any assumption of uniformity of illness causal beliefs within a community, even one that is relatively culturally homogeneous, is likely to be misleading. A better understanding of the diversity, and determinants, of illness causal beliefs can be of value in improving our understanding of illness experience, the clinical process, and in developing more effective health services and population health strategies.

Bilirubin and Stroke Risk Using a Mendelian Randomization Design.

PubMed

Lee, Sun Ju; Jee, Yon Ho; Jung, Keum Ji; Hong, Seri; Shin, Eun Soon; Jee, Sun Ha

2017-05-01

Circulating bilirubin, a natural antioxidant, is associated with decreased risk of stroke. However, the nature of the relationship between the two remains unknown. We used a Mendelian randomization analysis to assess the causal effect of serum bilirubin on stroke risk in Koreans. The 14 single-nucleotide polymorphisms (SNPs) (<10 -7 ) including rs6742078 of uridine diphosphoglucuronyl-transferase were selected from genome-wide association study of bilirubin level in the KCPS-II (Korean Cancer Prevention Study-II) Biobank subcohort consisting of 4793 healthy Korean and 806 stroke cases. Weighted genetic risk score was calculated using 14 SNPs selected from the top SNPs. Both rs6742078 (F statistics=138) and weighted genetic risk score with 14 SNPs (F statistics=187) were strongly associated with bilirubin levels. Simultaneously, serum bilirubin level was associated with decreased risk of stroke in an ordinary least-squares analysis. However, in 2-stage least-squares Mendelian randomization analysis, no causal relationship between serum bilirubin and stroke risk was found. There is no evidence that bilirubin level is causally associated with risk of stroke in Koreans. Therefore, bilirubin level is not a risk determinant of stroke. © 2017 American Heart Association, Inc.

Risk factors for unplanned pregnancy in women with mental illness living in a developing country.

PubMed

du Toit, Elsa; Jordaan, Esme; Niehaus, Dana; Koen, Liezl; Leppanen, Jukka

2018-06-01

Pregnant women in general are at an increased risk of experiencing symptoms of mental illness, and those living in a developing country are even more vulnerable. Research points towards a causal relationship between unplanned pregnancy and perinatal mental illness and suggests that pregnancy planning can aid in reducing the negative impact of mental illness on a woman, her unborn baby, and the rest of the family. In this quantitative, descriptive study, we investigated both socio-demographic factors and variables relating to mental illness itself that may place women at an increased risk of experiencing unplanned pregnancy. Data was gathered at two maternal mental health clinics in Cape Town by means of semi-structured interviews. Univariate analyses of the data revealed five independent key risk factors for unplanned pregnancy: lower levels of education, unmarried status, belonging to the Colored ethnic population, substance use, and having a history of two or more suicide attempts. Some of these factors overlap with findings of similar studies, but others are unique to the specific population (women with mental illness within a developing country). Screening of women based on these risk predictors may pave the way for early interventions and reduce the incidence of unplanned pregnancy and the negative consequences thereof in the South African population.

Causal inference in survival analysis using pseudo-observations.

PubMed

Andersen, Per K; Syriopoulou, Elisavet; Parner, Erik T

2017-07-30

Causal inference for non-censored response variables, such as binary or quantitative outcomes, is often based on either (1) direct standardization ('G-formula') or (2) inverse probability of treatment assignment weights ('propensity score'). To do causal inference in survival analysis, one needs to address right-censoring, and often, special techniques are required for that purpose. We will show how censoring can be dealt with 'once and for all' by means of so-called pseudo-observations when doing causal inference in survival analysis. The pseudo-observations can be used as a replacement of the outcomes without censoring when applying 'standard' causal inference methods, such as (1) or (2) earlier. We study this idea for estimating the average causal effect of a binary treatment on the survival probability, the restricted mean lifetime, and the cumulative incidence in a competing risks situation. The methods will be illustrated in a small simulation study and via a study of patients with acute myeloid leukemia who received either myeloablative or non-myeloablative conditioning before allogeneic hematopoetic cell transplantation. We will estimate the average causal effect of the conditioning regime on outcomes such as the 3-year overall survival probability and the 3-year risk of chronic graft-versus-host disease. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Human Papilloma Viruses and Breast Cancer - Assessment of Causality.

PubMed

Lawson, James Sutherland; Glenn, Wendy K; Whitaker, Noel James

2016-01-01

High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case-control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is "specificity." HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers.

Human Papilloma Viruses and Breast Cancer – Assessment of Causality

PubMed Central

Lawson, James Sutherland; Glenn, Wendy K.; Whitaker, Noel James

2016-01-01

High risk human papilloma viruses (HPVs) may have a causal role in some breast cancers. Case–control studies, conducted in many different countries, consistently indicate that HPVs are more frequently present in breast cancers as compared to benign breast and normal breast controls (odds ratio 4.02). The assessment of causality of HPVs in breast cancer is difficult because (i) the HPV viral load is extremely low, (ii) HPV infections are common but HPV associated breast cancers are uncommon, and (iii) HPV infections may precede the development of breast and other cancers by years or even decades. Further, HPV oncogenesis can be indirect. Despite these difficulties, the emergence of new evidence has made the assessment of HPV causality, in breast cancer, a practical proposition. With one exception, the evidence meets all the conventional criteria for a causal role of HPVs in breast cancer. The exception is “specificity.” HPVs are ubiquitous, which is the exact opposite of specificity. An additional reservation is that the prevalence of breast cancer is not increased in immunocompromised patients as is the case with respect to HPV-associated cervical cancer. This indicates that HPVs may have an indirect causal influence in breast cancer. Based on the overall evidence, high-risk HPVs may have a causal role in some breast cancers. PMID:27747193

Social-relational risk factors for predicting elder physical abuse: an ecological bi-focal model.

PubMed

von Heydrich, Levente; Schiamberg, Lawrence B; Chee, Grace

2012-01-01

Annually in the United States, 1 to 5 million older adults, 65 and above, are physically or sexually injured or mistreated by their caregivers in family settings. This study examined the prevalence and risk factors involved in elder physical abuse by adult child caregivers, moving from the immediate elderly parent/adult child relationship context to more distal social support contexts, utilizing a subsample of 203 elderly participants from the Midlife Development in the United States study (MIDUS II, 2004-2006). LISREL modeling examined causal pathways between elderly demographic characteristics, physical/emotional health, and behavioral and contextual characteristics from an ecological perspective. Data modeling was accomplished using Mplus, PAXW, and SYSTAT statistical software packages. Results indicate that latent factors including older adult health, social isolation of the older adult, and adult child characteristics were significantly associated with elder physical abuse, as mediated by the quality of the elderly parent/adult child relationship.

Does poor school performance cause later psychosocial problems among children in foster care? Evidence from national longitudinal registry data.

PubMed

Forsman, Hilma; Brännström, Lars; Vinnerljung, Bo; Hjern, Anders

2016-07-01

Research has shown that children in foster care are a high-risk group for adverse economic, social and health related outcomes in young adulthood. Children's poor school performance has been identified as a major risk factor for these poor later life outcomes. Aiming to support the design of effective intervention strategies, this study examines the hypothesized causal effect of foster children's poor school performance on subsequent psychosocial problems, here conceptualized as economic hardship, illicit drug use, and mental health problems, in young adulthood. Using the potential outcomes approach, longitudinal register data on more than 7500 Swedish foster children born 1973-1978 were analyzed by means of doubly robust treatment-effect estimators. The results show that poor school performance has a negative impact on later psychosocial problems net of observed background attributes and potential selection on unobservables, suggesting that the estimated effects allow for causal interpretations. Promotion of school performance may thus be a viable intervention path for policymakers and practitioners interested in improving foster children's overall life chances. Copyright © 2016 Elsevier Ltd. All rights reserved.

BioAge: Toward A Multi-Determined, Mechanistic Account of Cognitive Aging

PubMed Central

DeCarlo, Correne A.; Tuokko, Holly A.; Williams, Dorothy; Dixon, Roger A.; MacDonald, Stuart W.S.

2014-01-01

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. PMID:25278166

BioAge: toward a multi-determined, mechanistic account of cognitive aging.

PubMed

DeCarlo, Correne A; Tuokko, Holly A; Williams, Dorothy; Dixon, Roger A; MacDonald, Stuart W S

2014-11-01

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. Copyright © 2014 Elsevier B.V. All rights reserved.

Tobacco and cancer: epidemiology and new perspectives of prevention and monitoring in Mexico.

PubMed

Reynales-Shigematsu, Luz Myriam

2016-04-01

Tobacco smoking is causal risk factor of at least 16 different types of cancer. In Mexico, smoking causes 6 035 premature deaths annually of lung cancer and 5 154 from other types. Additionally, 16 408 new smoking- attributable cases are diagnosed, causing high costs in the Mexican health sector. The WHO Framework Convention on Tobacco Control is the global strategy to reduce morbidity and mortality caused by this risk factor. Four more cost-effective strategies to ensure the population benefit are: i) increase tobacco taxes, ii) create 100% smoke-free environments, iii) warn damage through health warnings with pictograms and iv) total ban of advertising and promotion. Mexico is call upon to implement with determination this comprehensive strategy to reduce cancer mortality and assuring the health population.

A literature review of neck pain associated with computer use: public health implications

PubMed Central

Green, Bart N

2008-01-01

Prolonged use of computers during daily work activities and recreation is often cited as a cause of neck pain. This review of the literature identifies public health aspects of neck pain as associated with computer use. While some retrospective studies support the hypothesis that frequent computer operation is associated with neck pain, few prospective studies reveal causal relationships. Many risk factors are identified in the literature. Primary prevention strategies have largely been confined to addressing environmental exposure to ergonomic risk factors, since to date, no clear cause for this work-related neck pain has been acknowledged. Future research should include identifying causes of work related neck pain so that appropriate primary prevention strategies may be developed and to make policy recommendations pertaining to prevention. PMID:18769599

Survival Bias When Assessing Risk Factors for Age-Related Macular Degeneration: A Tutorial with Application to the Exposure of Smoking.

PubMed

McGuinness, Myra B; Karahalios, Amalia; Kasza, Jessica; Guymer, Robyn H; Finger, Robert P; Simpson, Julie A

2017-08-01

We illustrate the effect of survival bias when investigating risk factors for eye disease in elderly populations for whom death is a competing risk. Our investigation focuses on the relationship between smoking and late age-related macular degeneration (AMD) in an observational study impacted by censoring due to death. Statistical methodology to calculate the survivor average causal effect (SACE) as a sensitivity analysis is described, including example statistical computing code for Stata and R. To demonstrate this method, we examine the causal effect of smoking history at baseline (1990-1994) on the presence of late AMD at the third study wave (2003-2007) using data from the Melbourne Collaborative Cohort Study. Of the 40,506 participants eligible for inclusion, 38,092 (94%) survived until the start of the third study wave, 20,752 (51%) were graded for AMD (60% female, aged 47-85 years, mean 65 ± 8.7 years). Late AMD was detected in 122 participants. Logistic regression showed strong evidence of an increased risk of late AMD for current smokers compared to non-smokers (adjusted naïve odds ratio 2.99, 95% confidence interval, CI, 1.74-5.13). Among participants expected to be alive at the start of follow-up regardless of their smoking status, the estimated SACE odds ratio comparing current smokers to non-smokers was at least 3.42 (95% CI 1.57-5.15). Survival bias can attenuate associations between harmful exposures and diseases of aging. Estimation of the SACE using a sensitivity analysis approach should be considered when conducting epidemiological research within elderly populations.

Is Helicobacter pylori really the cause of gastric cancer?

PubMed

Nyrén, O

1998-08-01

Since 1994, when the International Agency for Research on Cancer (IARC) designated Helicobacter pylori a human carcinogen, a considerable number of new studies have examined the association of this microorganism with risk of gastric cancer. The aim of this review was to critically evaluate current evidence of a causal relationship between the infection and gastric cancer in humans, taking these new studies into account. A MEDLINE search for the years 1982 through March 1998 yielded eight cohort studies, 40 case-control studies and eight ecologic studies. They were divided into four categories according to the weight of the evidence produced. In the category producing the strongest evidence, the cohort studies, five out of eight studies (including the three that formed the basis for the IARC decision) found a statistically significant excess risk of gastric cancer among the infected with odds ratios ranging between 2.8 and 6.0. Two cohort studies showed a non-significant tendency towards a positive association, but with point estimates indicating no more than a 50-60% excess risk among the H. pylori seropositive, and one apparently well-performed cohort study was completely negative. The two population-based case-control studies published to date found statistically non-significant odds ratios no higher than 1.3 and 1.4. Thus, the evidence of a strong causal link between H. pylori infection and gastric cancer has, if anything, become less convincing. Recent studies seem to indicate that the strength of the association may vary with type of H. pylori strain, and possibly presence of effect-modifying co-factors in the host and/or the environment. Future studies need to identify high-risk constellations of carcinogenic strains and unfavorable co-factors to make targeted prophylaxis cost-effective.

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

PubMed

Dunning, Alison M; Michailidou, Kyriaki; Kuchenbaecker, Karoline B; Thompson, Deborah; French, Juliet D; Beesley, Jonathan; Healey, Catherine S; Kar, Siddhartha; Pooley, Karen A; Lopez-Knowles, Elena; Dicks, Ed; Barrowdale, Daniel; Sinnott-Armstrong, Nicholas A; Sallari, Richard C; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Moradi Marjaneh, Mahdi; Lee, Jason S; Hills, Margaret; Jarosz, Monika; Drury, Suzie; Canisius, Sander; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Hopper, John L; Southey, Melissa C; Broeks, Annegien; Schmidt, Marjanka K; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W; Fasching, Peter A; Dos-Santos-Silva, Isabel; Peto, Julian; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; González-Neira, Anna; Perez, Jose I A; Anton-Culver, Hoda; Eunjung, Lee; Arndt, Volker; Brenner, Hermann; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Aittomäki, Kristiina; Blomqvist, Carl; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natasha; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-Chen; Wu, Anna H; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Henderson, Brian E; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Nord, Silje; Borresen-Dale, Anne-Lise; Kristensen, Vessela; Long, Jirong; Zheng, Wei; Pylkäs, Katri; Winqvist, Robert; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; Figueroa, Jonine; Sherman, Mark E; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; van den Ouweland, Ans M W; Humphreys, Keith; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Ghoussaini, Maya; Perkins, Barbara J; Shah, Mitul; Choi, Ji-Yeob; Kang, Daehee; Lee, Soo Chin; Hartman, Mikael; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Brennan, Paul; Sangrajrang, Suleeporn; Ambrosone, Christine B; Toland, Amanda E; Shen, Chen-Yang; Wu, Pei-Ei; Orr, Nick; Swerdlow, Anthony; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Kapuscinski, Miroslav; John, Esther M; Terry, Mary Beth; Daly, Mary B; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ejlertsen, Bent; Hansen, Thomas V O; Osorio, Ana; Benitez, Javier; Rando, Rachel; Weitzel, Jeffrey N; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Papi, Laura; Ottini, Laura; Konstantopoulou, Irene; Apostolou, Paraskevi; Garber, Judy; Rashid, Muhammad Usman; Frost, Debra; Izatt, Louise; Ellis, Steve; Godwin, Andrew K; Arnold, Norbert; Niederacher, Dieter; Rhiem, Kerstin; Bogdanova-Markov, Nadja; Sagne, Charlotte; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Sinilnikova, Olga M; Mazoyer, Sylvie; Isaacs, Claudine; Claes, Kathleen B M; De Leeneer, Kim; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Khan, Sofia; Mensenkamp, Arjen R; Hooning, Maartje J; Rookus, Matti A; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Pujana, Miquel Angel; Gronwald, Jacek; Huzarski, Tomasz; Barkardottir, Rosa B; Laframboise, Rachel; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R; Park, Sue Kyung; Lindor, Noralane; Couch, Fergus J; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Singer, Christian F; Rappaport, Christine; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Hulick, Peter J; Phillips, Kelly-Anne; Piedmonte, Marion; Mulligan, Anna Marie; Glendon, Gord; Bojesen, Anders; Thomassen, Mads; Caligo, Maria A; Yoon, Sook-Yee; Friedman, Eitan; Laitman, Yael; Borg, Ake; von Wachenfeldt, Anna; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I; Ganz, Patricia A; Nussbaum, Robert L; Gayther, Simon A; Nathanson, Katherine L; Domchek, Susan M; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Maskarinec, Gertraud; Woolcott, Christy; Scott, Christopher; Stone, Jennifer; Apicella, Carmel; Tamimi, Rulla; Luben, Robert; Khaw, Kay-Tee; Helland, Åslaug; Haakensen, Vilde; Dowsett, Mitch; Pharoah, Paul D P; Simard, Jacques; Hall, Per; García-Closas, Montserrat; Vachon, Celine; Chenevix-Trench, Georgia; Antoniou, Antonis C; Easton, Douglas F; Edwards, Stacey L

2016-04-01

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

PubMed Central

Dunning, Alison M; Michailidou, Kyriaki; Kuchenbaecker, Karoline B; Thompson, Deborah; French, Juliet D; Beesley, Jonathan; Healey, Catherine S; Kar, Siddhartha; Pooley, Karen A; Lopez-Knowles, Elena; Dicks, Ed; Barrowdale, Daniel; Sinnott-Armstrong, Nicholas A; Sallari, Richard C; Hillman, Kristine M; Kaufmann, Susanne; Sivakumaran, Haran; Marjaneh, Mahdi Moradi; Lee, Jason S; Hills, Margaret; Jarosz, Monika; Drury, Suzie; Canisius, Sander; Bolla, Manjeet K; Dennis, Joe; Wang, Qin; Hopper, John L; Southey, Melissa C; Broeks, Annegien; Schmidt, Marjanka K; Lophatananon, Artitaya; Muir, Kenneth; Beckmann, Matthias W; Fasching, Peter A; dos-Santos-Silva, Isabel; Peto, Julian; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marme, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; González-Neira, Anna; Perez, Jose I A; Anton-Culver, Hoda; Eunjung, Lee; Arndt, Volker; Brenner, Hermann; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Aittomäki, Kristiina; Blomqvist, Carl; Ito, Hidemi; Matsuo, Keitaro; Bogdanova, Natasha; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Kosma, Veli-Matti; Mannermaa, Arto; Tseng, Chiu-chen; Wu, Anna H; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Peterlongo, Paolo; Radice, Paolo; Olson, Janet E; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Henderson, Brian E; Goldberg, Mark S; Teo, Soo H; Yip, Cheng Har; Nord, Silje; Borresen-Dale, Anne-Lise; Kristensen, Vessela; Long, Jirong; Zheng, Wei; Pylkäs, Katri; Winqvist, Robert; Andrulis, Irene L; Knight, Julia A; Devilee, Peter; Seynaeve, Caroline; Figueroa, Jonine; Sherman, Mark E; Czene, Kamila; Darabi, Hatef; Hollestelle, Antoinette; van den Ouweland, Ans M W; Humphreys, Keith; Gao, Yu-Tang; Shu, Xiao-Ou; Cox, Angela; Cross, Simon S; Blot, William; Cai, Qiuyin; Ghoussaini, Maya; Perkins, Barbara J; Shah, Mitul; Choi, Ji-Yeob; Kang, Daehee; Lee, Soo Chin; Hartman, Mikael; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Brennan, Paul; Sangrajrang, Suleeporn; Ambrosone, Christine B; Toland, Amanda E; Shen, Chen-Yang; Wu, Pei-Ei; Orr, Nick; Swerdlow, Anthony; McGuffog, Lesley; Healey, Sue; Lee, Andrew; Kapuscinski, Miroslav; John, Esther M; Terry, Mary Beth; Daly, Mary B; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M; van Rensburg, Elizabeth J; Neuhausen, Susan L; Ejlertsen, Bent; Hansen, Thomas V O; Osorio, Ana; Benitez, Javier; Rando, Rachel; Weitzel, Jeffrey N; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Papi, Laura; Ottini, Laura; Konstantopoulou, Irene; Apostolou, Paraskevi; Garber, Judy; Rashid, Muhammad Usman; Frost, Debra; Izatt, Louise; Ellis, Steve; Godwin, Andrew K; Arnold, Norbert; Niederacher, Dieter; Rhiem, Kerstin; Bogdanova-Markov, Nadja; Sagne, Charlotte; Stoppa-Lyonnet, Dominique; Damiola, Francesca; Sinilnikova, Olga M; Mazoyer, Sylvie; Isaacs, Claudine; Claes, Kathleen B M; De Leeneer, Kim; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Khan, Sofia; Mensenkamp, Arjen R; Hooning, Maartje J; Rookus, Matti A; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Pujana, Miquel Angel; Gronwald, Jacek; Huzarski, Tomasz; Barkardottir, Rosa B; Laframboise, Rachel; Soucy, Penny; Montagna, Marco; Agata, Simona; Teixeira, Manuel R; Park, Sue Kyung; Lindor, Noralane; Couch, Fergus J; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Singer, Christian F; Rappaport, Christine; Phelan, Catherine M; Greene, Mark H; Mai, Phuong L; Rennert, Gad; Imyanitov, Evgeny N; Hulick, Peter J; Phillips, Kelly-Anne; Piedmonte, Marion; Mulligan, Anna Marie; Glendon, Gord; Bojesen, Anders; Thomassen, Mads; Caligo, Maria A; Yoon, Sook-Yee; Friedman, Eitan; Laitman, Yael; Borg, Ake; von Wachenfeldt, Anna; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I; Ganz, Patricia A; Nussbaum, Robert L; Gayther, Simon A; Nathanson, Katherine L; Domchek, Susan M; Arun, Banu K; Mitchell, Gillian; Karlan, Beth Y; Lester, Jenny; Maskarinec, Gertraud; Woolcott, Christy; Scott, Christopher; Stone, Jennifer; Apicella, Carmel; Tamimi, Rulla; Luben, Robert; Khaw, Kay-Tee; Helland, Åslaug; Haakensen, Vilde; Dowsett, Mitch; Pharoah, Paul D P; Simard, Jacques; Hall, Per; García-Closas, Montserrat; Vachon, Celine; Chenevix-Trench, Georgia; Antoniou, Antonis C; Easton, Douglas F; Edwards, Stacey L

2016-01-01

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER+ or ER−) and human ERBB2 (HER2+ or HER2−) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER− tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression. PMID:26928228

Possible risk factors for increased suicide following bariatric surgery.

PubMed

Mitchell, James E; Crosby, Ross; de Zwaan, Martina; Engel, Scott; Roerig, James; Steffen, Kristine; Gordon, Kathryn H; Karr, Trisha; Lavender, Jason; Wonderlich, Steve

2013-04-01

There is a growing research literature suggesting that there may be elevated risk of suicide following bariatric surgery. Most of the data reported thus far has been cross-sectional and observational, and very little is known about the possible specific causal variables involved. The purpose of this report is to review this literature and to review possible risk factors for increased suicidal risk following bariatric surgery, to delineate future research directions. First a variety of medical, biological, and genetic factors, including the persistence or recurrence of medical comorbidities after bariatric surgery, the disinhibition and impulsivity secondary to changes in the absorption of alcohol, hypoglycemia, as well as pharmacokinetic changes that may affect the absorption of various medications including antidepressant medications are reviewed. Also reviewed are possible mediating factors involving changes in various peptidergic systems such as GLP-1 and Ghrelin. A number of psychosocial issues that might be involved are discussed, including lack of improvement in quality of life after surgery, continued or recurrent physical mobility restrictions, persistence or recurrence of sexual dysfunction and relationship problems, low self-esteem, and a history of child maltreatment. Inadequate weight loss or weight regain are also discussed. A number of possible contributing factors have been identified. Possible theoretical models involved and directions for research are suggested. Copyright © 2012 The Obesity Society.

Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

PubMed Central

Vigorito, Elena; Kuchenbaecker, Karoline B.; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A.; Andrulis, Irene L.; Arun, Banu K.; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A.; Campbell, Ian; Chan, Salina B.; Claes, Kathleen B. M.; Cohn, David E.; Cook, Jackie; Daly, Mary B.; Damiola, Francesca; Davidson, Rosemarie; de Pauw, Antoine; Delnatte, Capucine; Diez, Orland; Domchek, Susan M.; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F.; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D. Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D.; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A.; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K.; Goldgar, David E.; Hake, Christopher R.; Hansen, Thomas V. O.; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B. L.; Houdayer, Claude; Hulick, Peter J.; Imyanitov, Evgeny N.; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M.; Vijai, Joseph; Karlan, Beth Y.; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L.; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R.; Montagna, Marco; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I.; Ong, Kai-ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C.; Rookus, Matti A.; Ross, Eric A.; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F.; Slavin, Thomas P.; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I.; Tea, Muy-Kheng; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J.; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N.; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J.; Greene, Mark H.; Couch, Fergus J.; Offit, Kenneth; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Antoniou, Antonis C.

2016-01-01

Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10−16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10−6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population. PMID:27463617

Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

PubMed

Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan; Adlard, Julian; Agnarsson, Bjarni A; Andrulis, Irene L; Arun, Banu K; Barjhoux, Laure; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Bojesen, Anders; Bonanni, Bernardo; Brewer, Carole; Caldes, Trinidad; Caligo, Maria A; Campbell, Ian; Chan, Salina B; Claes, Kathleen B M; Cohn, David E; Cook, Jackie; Daly, Mary B; Damiola, Francesca; Davidson, Rosemarie; Pauw, Antoine de; Delnatte, Capucine; Diez, Orland; Domchek, Susan M; Dumont, Martine; Durda, Katarzyna; Dworniczak, Bernd; Easton, Douglas F; Eccles, Diana; Edwinsdotter Ardnor, Christina; Eeles, Ros; Ejlertsen, Bent; Ellis, Steve; Evans, D Gareth; Feliubadalo, Lidia; Fostira, Florentia; Foulkes, William D; Friedman, Eitan; Frost, Debra; Gaddam, Pragna; Ganz, Patricia A; Garber, Judy; Garcia-Barberan, Vanesa; Gauthier-Villars, Marion; Gehrig, Andrea; Gerdes, Anne-Marie; Giraud, Sophie; Godwin, Andrew K; Goldgar, David E; Hake, Christopher R; Hansen, Thomas V O; Healey, Sue; Hodgson, Shirley; Hogervorst, Frans B L; Houdayer, Claude; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jacobs, Lauren; Jakubowska, Anna; Janavicius, Ramunas; Jaworska-Bieniek, Katarzyna; Jensen, Uffe Birk; John, Esther M; Vijai, Joseph; Karlan, Beth Y; Kast, Karin; Investigators, KConFab; Khan, Sofia; Kwong, Ava; Laitman, Yael; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Lubinski, Jan; Mai, Phuong L; Manoukian, Siranoush; Mazoyer, Sylvie; Meindl, Alfons; Mensenkamp, Arjen R; Montagna, Marco; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Niederacher, Dieter; Olah, Edith; Olopade, Olufunmilayo I; Ong, Kai-Ren; Osorio, Ana; Park, Sue Kyung; Paulsson-Karlsson, Ylva; Pedersen, Inge Sokilde; Peissel, Bernard; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Piedmonte, Marion; Poppe, Bruce; Pujana, Miquel Angel; Radice, Paolo; Rennert, Gad; Rodriguez, Gustavo C; Rookus, Matti A; Ross, Eric A; Schmutzler, Rita Katharina; Simard, Jacques; Singer, Christian F; Slavin, Thomas P; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stoppa-Lyonnet, Dominique; Sukiennicki, Grzegorz; Sutter, Christian; Szabo, Csilla I; Tea, Muy-Kheng; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; van Rensburg, Elizabeth J; Varesco, Liliana; Varon-Mateeva, Raymonda; Vratimos, Athanassios; Weitzel, Jeffrey N; McGuffog, Lesley; Kirk, Judy; Toland, Amanda Ewart; Hamann, Ute; Lindor, Noralane; Ramus, Susan J; Greene, Mark H; Couch, Fergus J; Offit, Kenneth; Pharoah, Paul D P; Chenevix-Trench, Georgia; Antoniou, Antonis C

2016-01-01

Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

C-reactive protein and cardiovascular risk in bipolar disorder patients: A systematic review.

PubMed

Marshe, Victoria S; Pira, Shamira; Mantere, Outi; Bosche, Bert; Looper, Karl J; Herrmann, Nathan; Müller, Daniel J; Rej, Soham

2017-10-03

New research is revealing a strong association between inflammatory markers with bipolar disorder (BD), potentially due to the high prevalence of cardiovascular disease and cardiovascular risk factors in BD. We aimed to synthesize the literature examining the association between the clinically most relevant inflammatory marker, C-reactive protein (CRP) and cardiovascular disease and cardiovascular risk factors in patients with BD. MEDLINE, Embase and PsychInfo were systematically searched for all relevant English language articles published prior to April 2017. Articles were included if they examined the association between CRP and cardiovascular risk factors/disease in BD. Fifteen relevant articles were retrieved. Studies were mostly cross-sectional and heterogeneous in the cardiovascular risk factors investigated. Overall, elevated CRP was associated with increased risk of metabolic syndrome, elevated body mass index, higher waist circumference, and obesity. CRP was inconsistently associated with elevated fasting glucose, insulin levels, serum triglycerides, total cholesterol levels, and low high density lipoprotein (HDL) levels. Atypical antipsychotic use may mediate some of these effects. No study examined CRP's association with actual cardiovascular disease (e.g. coronary artery disease) in BD. In BD, CRP is associated with increases in several cardiovascular risk factors, suggesting that systemic inflammation could be a shared driving force for both outcomes of BD and cardiovascular risk. Further longitudinal research is needed in this area to verify causality, including an examination of actual cardiovascular disease. Non-pharmacological and pharmacological treatments with anti-inflammatory effects should also be investigated, particularly in patients with increased CRP, for their potential to reduce cardiovascular risk in BD. Copyright © 2017 Elsevier Inc. All rights reserved.

DNA methylation as a potential mediator of environmental risks in the development of childhood acute lymphoblastic leukemia

PubMed Central

Timms, Jessica A; Relton, Caroline L; Rankin, Judith; Strathdee, Gordon; McKay, Jill A

2016-01-01

5-year survival rate for childhood acute lymphoblastic leukemia (ALL) has risen to approximately 90%, yet the causal disease pathway is still poorly understood. Evidence suggests multiple ‘hits’ are required for disease progression; an initial genetic abnormality followed by additional secondary ‘hits’. It is plausible that environmental influences may trigger these secondary hits, and with the peak incidence of diagnosis between 2 and 5 years of age, early life exposures are likely to be key. DNA methylation can be modified by many environmental exposures and is dramatically altered in cancers, including childhood ALL. Here we explore the potential that DNA methylation may be involved in the causal pathway toward disease by acting as a mediator between established environmental factors and childhood ALL development. PMID:27035209

Narrative review of yoga intervention clinical trials including weight-related outcomes.

PubMed

Rioux, Jennifer Grace; Ritenbaugh, Cheryl

2013-01-01

Medical authorities have identified obesity as a causal factor in the development of diabetes, hypertension, and cardiovascular disease (CVD), and more broadly, of metabolic syndrome/insulin resistance syndrome. To provide solutions that can modify this risk factor, researchers need to identify methods of effective risk reduction and primary prevention of obesity. Research on the effectiveness of yoga as a treatment for obesity is limited, and studies vary in overall quality and methodological rigor. This narrative review assessed the quantity and quality of clinical trials of yoga as an intervention for weight loss or as a means of risk reduction or treatment for obesity and diseases in which obesity is a causal factor. This review summarized the studies' research designs and evaluated the efficacy of yoga for weight loss via the current evidence base. The research team evaluated published studies to determine the appropriateness of research designs, comparability of programs' intervention elements, and standardization of outcome measures. The research team's literature search used the key terms yoga and obesity or yoga and weight loss in three primary medical-literature databases (PubMed, PsychInfo, and Web of Science). The study excluded clinical trials with no quantitative obesity related measure. Extracted data included each study's (1) design; (2) setting and population; (3) nature, duration, and frequency of interventions; (4) comparison groups; (5) recruitment strategies; (6) outcome measures; (7) data analysis and presentation; and (8) results and conclusions. The research team developed an overall evaluation parameter to compare disparate trials. The research team reviewed each study to determine its key features, each worth a specified number of points, with a maximum total of 20 points. The features included a study's (1) duration, (2) frequency of yoga practice, (3) intensity of (length of) each practice, (4) number of yogic elements, (5) inclusion of dietary modification, (6) inclusion of a residential component, (7) the number of weight-related outcome measures, and (8) a discussion of the details of the yogic elements. Overall, therapeutic yoga programs are frequently effective in promoting weight loss and/or improvements in body composition. The effectiveness of yoga for weight loss is related to the following key features: (1) an increased frequency of practice; (2) a longer intervention duration (3) a yogic dietary component; (4) a residential component; (5) the comprehensive inclusion of yogic components; (5) and a home-practice component. Yoga appears to be an appropriate and potentially successful intervention for weight maintenance, prevention of obesity, and risk reduction for diseases in which obesity plays a significant causal role.

Causal chain analysis and root causes: the GIWA approach.

PubMed

Belausteguigoitia, Juan Carlos

2004-02-01

The Global International Waters Assessment (GIWA) was created to help develop a priority setting mechanism for actions in international waters. Apart from assessing the severity of environmental problems in ecosystems, the GIWA's task is to analyze potential policy actions that could solve or mitigate these problems. Given the complex nature of the problems, understanding their root causes is essential to develop effective solutions. The GIWA provides a framework to analyze these causes, which is based on identifying the factors that shape human behavior in relation to the use (direct or indirect) of aquatic resources. Two sets of factors are analyzed. The first one consists of social coordination mechanisms (institutions). Faults in these mechanisms lead to wasteful use of resources. The second consists of factors that do not cause wasteful use of resources per se (poverty, trade, demographic growth, technology), but expose and magnify the faults of the first group of factors. The picture that comes out is that diagnosing simple generic causes, e.g. poverty or trade, without analyzing the case specific ways in which the root causes act and interact to degrade the environment, will likely ignore important links that may put the effectiveness of the recommended policies at risk. A summary of the causal chain analysis for the Colorado River Delta is provided as an example.

Long-Term Consequences of Early Sexual Initiation on Young Adult Health: A Causal Inference Approach

ERIC Educational Resources Information Center

Kugler, Kari C.; Vasilenko, Sara A.; Butera, Nicole M.; Coffman, Donna L.

2017-01-01

Although early sexual initiation has been linked to negative outcomes, it is unknown whether these effects are causal. In this study, we use propensity score methods to estimate the causal effect of early sexual initiation on young adult sexual risk behaviors and health outcomes using data from the National Longitudinal Study of Adolescent to…

Understanding environmental contributions to autism: Causal concepts and the state of science.

PubMed

Hertz-Picciotto, Irva; Schmidt, Rebecca J; Krakowiak, Paula

2018-04-01

The complexity of neurodevelopment, the rapidity of early neurogenesis, and over 100 years of research identifying environmental influences on neurodevelopment serve as backdrop to understanding factors that influence risk and severity of autism spectrum disorder (ASD). This Keynote Lecture, delivered at the May 2016 annual meeting of the International Society for Autism Research, describes concepts of causation, outlines the trajectory of research on nongenetic factors beginning in the 1960s, and briefly reviews the current state of this science. Causal concepts are introduced, including root causes; pitfalls in interpreting time trends as clues to etiologic factors; susceptible time windows for exposure; and implications of a multi-factorial model of ASD. An historical background presents early research into the origins of ASD. The epidemiologic literature from the last fifteen years is briefly but critically reviewed for potential roles of, for example, air pollution, pesticides, plastics, prenatal vitamins, lifestyle and family factors, and maternal obstetric and metabolic conditions during her pregnancy. Three examples from the case-control CHildhood Autism Risks from Genes and the Environment Study are probed to illustrate methodological approaches to central challenges in observational studies: capturing environmental exposure; causal inference when a randomized controlled clinical trial is either unethical or infeasible; and the integration of genetic, epigenetic, and environmental influences on development. We conclude with reflections on future directions, including exposomics, new technologies, the microbiome, gene-by-environment interaction in the era of -omics, and epigenetics as the interface of those two. As the environment is malleable, this research advances the goal of a productive and fulfilling life for all children, teen-agers and adults. Autism Res 2018, 11: 554-586. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. This Keynote Lecture, delivered at the 2016 meeting of the International Society for Autism Research, discusses evidence from human epidemiologic studies of prenatal factors contributing to autism, such as pesticides, maternal nutrition and her health. There is no single cause for autism. Examples highlight the features of a high-quality epidemiology study, and what comprises a compelling case for causation. Emergent research directions hold promise for identifying potential interventions to reduce disabilities, enhance giftedness, and improve lives of those with ASD. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Risk factor studies of age-at-onset in a sample ascertained for Parkinson disease affected sibling pairs: a cautionary tale

PubMed Central

Wilk, Jemma B; Lash, Timothy L

2007-01-01

An association between exposure to a risk factor and age-at-onset of disease may reflect an effect on the rate of disease occurrence or an acceleration of the disease process. The difference in age-at-onset arising from case-only studies, however, may also reflect secular trends in the prevalence of exposure to the risk factor. Comparisons of age-at-onset associated with risk factors are commonly performed in case series enrolled for genetic linkage analysis of late onset diseases. We describe how the results of age-at-onset studies of environmental risk factors reflect the underlying structure of the source population, rather than an association with age-at-onset, by contrasting the effects of coffee drinking and cigarette smoking on Parkinson disease age-at-onset with the effects on age-at-enrollment in a population based study sample. Despite earlier evidence to suggest a protective association of coffee drinking and cigarette smoking with Parkinson disease risk, the age-at-onset results are comparable to the patterns observed in the population sample, and thus a causal inference from the age-at-onset effect may not be justified. Protective effects of multivitamin use on PD age-at-onset are also shown to be subject to a bias from the relationship between age and multivitamin initiation. Case-only studies of age-at-onset must be performed with an appreciation for the association between risk factors and age and ageing in the source population. PMID:17408493

Causal attribution for success and failure in mathematics among MDAB pre-diploma students

NASA Astrophysics Data System (ADS)

Maidinsah, Hamidah; Embong, Rokiah; Wahab, Zubaidah Abd

2014-07-01

The Program Mengubah Destini Anak Bangsa (MDAB) is a pre-diploma programme catering to SPM school leavers who do not meet the minimum requirement to enter any of UiTM diploma programmes. The study aims to evaluate the perceptions of MDAB students toward the main causal attribution factors underlying students' success and failure in mathematics. Research sample comprised of 482 students from five UiTM branch campuses. Research instrument used was a set of GALUS questionnaire consisting of 36 items based on the Weiner Attribution Theory. Four causal attributions factors for success and failures evaluated are ability, effort, question difficulty and environment. GALUS reliability index was 0.93. The research found that effort appears to be the main causal attribution factor in students' success and failure in mathematics, followed by environment, question difficulty and ability. High achiever students strongly agree that the ability factor influenced their success while low achiever students strongly agree that all attributing factors influenced their failures in mathematics.

NON-MENDELIAN ETIOLOGIC FACTORS IN NEUROPSYCHIATRIC ILLNESS: PLEIOTROPY, EPIGENETICS, AND CONVERGENCE

PubMed Central

Deutsch, Curtis K; McIlvane, William J

2013-01-01

The target article by Charney on behavior genetics/genomics discusses how numerous molecular factors can inform heritability estimations and genetic association studies. These factors find application in the search for genes for behavioral phenotypes, including neuropsychiatric disorders. We elaborate upon how single causal factors can generate multiple phenotypes, and discuss how multiple causal factors may converge on common neurodevelopmental mechanisms. PMID:23095384

Dental Students' Perceptions of Risk Factors for Musculoskeletal Disorders: Adapting the Job Factors Questionnaire for Dentistry.

PubMed

Presoto, Cristina D; Wajngarten, Danielle; Domingos, Patrícia A S; Campos, Juliana A D B; Garcia, Patrícia P N S

2018-01-01

The aims of this study were to adapt the Job Factors Questionnaire to the field of dentistry, evaluate its psychometric properties, evaluate dental students' perceptions of work/study risk factors for musculoskeletal disorders, and determine the influence of gender and academic level on those perceptions. All 580 students enrolled in two Brazilian dental schools in 2015 were invited to participate in the study. A three-factor structure (Repetitiveness, Work Posture, and External Factors) was tested through confirmatory factor analysis. Convergent validity was estimated using the average variance extracted (AVE), discriminant validity was based on the correlational analysis of the factors, and reliability was assessed. A causal model was created using structural equation modeling to evaluate the influence of gender and academic level on students' perceptions. A total of 480 students completed the questionnaire for an 83% response rate. The responding students' average age was 21.6 years (SD=2.98), and 74.8% were women. Higher scores were observed on the Work Posture factor items. The refined model presented proper fit to the studied sample. Convergent validity was compromised only for External Factors (AVE=0.47), and discriminant validity was compromised for Work Posture and External Factors (r 2 =0.69). Reliability was adequate. Academic level did not have a significant impact on the factors, but the women students exhibited greater perception. Overall, the adaptation resulted in a useful instrument for assessing perceptions of risk factors for musculoskeletal disorders. Gender was found to significantly influence all three factors, with women showing greater perception of the risk factors.

The thermolabile variant of MTHFR is associated with depression in the British Women's Heart and Health Study and a meta-analysis.

PubMed

Lewis, S J; Lawlor, D A; Davey Smith, G; Araya, R; Timpson, N; Day, I N M; Ebrahim, S

2006-04-01

Low dietary folate intake has been implicated as a risk factor for depression. However, observational epidemiological studies are plagued by problems of confounding, reverse causality and measurement error. A common polymorphism (C677T) in MTHFR is associated with methyltetrahydrofolate reductase (MTHFR) activity and circulating folate and homocysteine levels and offers insights into whether the association between low folate and depression is causal. We genotyped this polymorphism in 3,478 women in the British Women's Heart and Health Study. In these women, we looked at the association between genotype and three indicators of depression; ever diagnosed as depressed, currently taking antidepressants and the EuroQol mood question. We also carried out a systematic review and meta-analysis of all published studies which have looked at the association between MTHFR C677T genotype and depression. In the British Women's Heart and Health Study, we found evidence of an increased risk of ever being diagnosed as depressed in MTHFR C677T TT individuals compared with CC individuals, odds ratio (OR) 1.35(95% CI: 1.01, 1.80). Furthermore, we identified eight other studies, which have examined the association between depression and MTHFR C677T. We were able to include all of these studies in our meta-analysis together with our results, obtaining an overall summary OR of 1.36 (95% CI: 1.11, 1.67, P=0.003). Since this genotype influences the functioning of the folate metabolic pathway, these findings suggest that folate or its derivatives may be causally related to risk of depression. Molecular Psychiatry (2006) 11, 352-360. doi:10.1038/sj.mp.4001790; published online 10 January 2006.

Vasectomy and prostate cancer risk: a historical synopsis of undulating false causality.

PubMed

Nutt, Max; Reed, Zachary; Köhler, Tobias S

2016-01-01

The potential influence of vasectomy being a risk factor for the development of prostate cancer is not a new concept, with more than 30 publications addressing the topic. Given the global frequency of vasectomy and the prevalence of prostate cancer, this subject justifiably deserves scrutiny. Several articles have claimed that vasectomy puts men at risk for future development of prostate cancer. We explore articles that have shown the contrary (no link), explore the studies' strengths and weaknesses, describe possible prostate cancer pathophysiologic mechanisms, and apply Bradford Hill criteria to help discern correlation with causation. The risk and interest of association of prostate cancer with vasectomy has waxed and waned over the last three decades. Based on our review, vasectomy remains a safe form of sterilization and does not increase prostate cancer risk.

Risk assessment and causal preventive measures.

PubMed

Lussi, Adrian; Hellwig, Elmar

2014-01-01

A prerequisite for preventive measures is to diagnose erosive tooth wear and to evaluate the different etiological factors in order to identify persons at risk. No diagnostic device is available for the assessment of erosive defects. Thus, they can only be detected clinically. Consequently, erosion not diagnosed at an early stage may render timely preventive measures difficult. In order to assess the risk factors, patients should record their dietary intake for a distinct period of time. Then a dentist can determine the erosive potential of the diet. A table with common beverages and foodstuffs is presented for judging the erosive potential. Particularly, patients with more than 4 dietary acid intakes have a higher risk for erosion when other risk factors are present. Regurgitation of gastric acids is a further important risk factor for the development of erosion which has to be taken into account. Based on these analyses, an individually tailored preventive program may be suggested to the patients. It may comprise dietary advice, use of calcium-enriched beverages, optimization of prophylactic regimes, stimulation of salivary flow rate, use of buffering medicaments and particular motivation for nondestructive toothbrushing habits with an erosive-protecting toothpaste as well as rinsing solutions. Since erosion and abrasion often occur simultaneously, all of the causative components must be taken into consideration when planning preventive strategies but only those important and feasible for an individual should be communicated to the patient. © 2014 S. Karger AG, Basel.

Stable Causal Relationships Are Better Causal Relationships.

PubMed

Vasilyeva, Nadya; Blanchard, Thomas; Lombrozo, Tania

2018-05-01

We report three experiments investigating whether people's judgments about causal relationships are sensitive to the robustness or stability of such relationships across a range of background circumstances. In Experiment 1, we demonstrate that people are more willing to endorse causal and explanatory claims based on stable (as opposed to unstable) relationships, even when the overall causal strength of the relationship is held constant. In Experiment 2, we show that this effect is not driven by a causal generalization's actual scope of application. In Experiment 3, we offer evidence that stable causal relationships may be seen as better guides to action. Collectively, these experiments document a previously underappreciated factor that shapes people's causal reasoning: the stability of the causal relationship. Copyright © 2018 Cognitive Science Society, Inc.

Hippocampus and amygdala volumes in children and young adults at high-risk of schizophrenia: research synthesis.

PubMed

Ganzola, Rossana; Maziade, Michel; Duchesne, Simon

2014-06-01

Studies have reported hippocampal and amygdala volume abnormalities in schizophrenic patients. It is necessary to explore the potential for these structures as early disease markers in subjects at high risk (HR) of schizophrenia. We performed a review of 29 magnetic resonance imaging (MRI) studies measuring hippocampal and amygdala volumes in subjects at HR for schizophrenia. We reclassified subjects in 3 new HR categories: presence of only risk symptoms (psychotic moderate symptoms), presence of only risk factors (genetic, developmental or environmental), and presence of combined risk symptoms/factors. Hippocampal volume reductions were detected in subjects with first episode (FE) of psychosis, in all young adults and in adolescents at HR of schizophrenia. The loss of tissue was mainly located in the posterior part of hippocampus and the right side seems more vulnerable in young adults with only risk symptoms. Instead, the anterior sector seems more involved in HR subjects with genetic risks. Abnormal amygdala volumes were found in FE subjects, in children with combined risk symptoms/factors and in older subjects using different inclusion criteria, but not in young adults. Hippocampal and amygdala abnormalities may be present before schizophrenia onset. Further studies should be conducted to clarify whether these abnormalities are causally or effectually related to neurodevelopment. Shape analysis could clarify the impact of environmental, genetic, and developmental factors on the medial temporal structures during the evolution of this disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?

PubMed Central

Gibelin, Aude; de Prost, Nicolas; Brun-Buisson, Christian

2013-01-01

Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy. PMID:23964048

Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?

PubMed

Gibelin, Aude; de Prost, Nicolas; Brun-Buisson, Christian

2013-08-20

Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy.

[Family environment risk factors of depression in adolescence].

PubMed

Greszta, Elzbieta

2006-01-01

General psychosocial theories of developmental psychopathology assert that family environment plays a significant role in forming both adaptive and maladaptive functioning of children. Also virtually all theories of depression assert that faulty parent-child relationships play a major role in the aetiology of this disorder. According these theoretical formulations familial risk factors have been the focus of most research on depression in adolescence. Several studies have shown that insecure attachment and parenting characterized by coldness, rejection, harsh discipline and unsupportive behaviour is positively related to adolescent depressive symptoms. Some research indicates that authoritative parenting, conceptualized as a composite of warmth, accept-involvement, firm control, and democratic discipline, is associated with the least depressive symptoms among adolescents. Pathogenetic factors within the family environment, such as parental depression, changes of family structure, violence or neglect, can also contribute to depression in adolescence. A causal relationship between anomalous parenting and depression is probably the interplay among genetic, cognitive, emotional, interpersonal and family environmental factors.

Do Child Abuse and Maltreatment Increase Risk of Schizophrenia?

PubMed Central

Sideli, Lucia; Mule, Alice; La Barbera, Daniele

2012-01-01

Introduction IntroductionaaAlthough childhood abuse is a recognised risk factor for depression, post-traumatic stress disorder, and substance misuse, its role in the aetiology of psychotic disorder remained controversial. This is in part because the putative effect of childhood trauma on psychosis has been mostly evaluated by small, cross sectional, uncontrolled studies that raised methodological issues. Methods Papers concerning the association between childhood trauma and psychotic disorders (to November, 2011) were identified using a comprehensive search of PubMed, Psychinfo, and Scopus and analysing reference list of relevant papers. A narrative synthesis was used to summarise results. Results An association between childhood abuse and psychotic symptoms was consistently reported by large cross sectional surveys with an effect ranging from 1.7 to 15. However, we cannot conclude that the relationship is causal as lack of longitudinal studies prevent us from fully excluding alternative explanations such as reverse causality. Gender, cannabis use, and depressive and post-traumatic stress disorder symptoms appear to moderate the effect of childhood trauma on psychotic disorders. However, specificity of childhood abuse in psychotic disorders and, particularly, in schizophrenia has not been demonstrated. Conclusion Although the association between childhood abuse and psychosis has been replicated, the etiological role of such early adversity has yet to be fully clarified. So far none of the studies reported support the hypothesis that childhood abuse is either sufficient or necessary to develop a psychotic disorder. It seems likely that any effect of childhood abuse on schizophrenia needs to be understood in terms of genetic susceptibility and interaction with other environmental risk factors. PMID:22707958

Smoking and subsequent human papillomavirus infection: a mediation analysis.

PubMed

Eldridge, Ronald C; Pawlita, Michael; Wilson, Lauren; Castle, Philip E; Waterboer, Tim; Gravitt, Patti E; Schiffman, Mark; Wentzensen, Nicolas

2017-11-01

Smoking is an established risk factor for a human papillomavirus (HPV) infection advancing to cervical precancer and cancer, but its role earlier in the natural history is less clear. Smoking is inversely associated with possessing HPV antibodies from a past infection suggesting that smoking may influence acquiring subsequent infections. In a cohort of 1976 U.S. women, we evaluate whether reduced antibodies to HPV-16 is a mechanism for smoking's role on acquiring a subsequent HPV-16 infection, through the analytic technique of causal mediation analysis. We posit a causal model and estimate two counterfactually defined effects: a smoking impaired antibody-mediated indirect effect and a nonmediated direct effect representing all other potential mechanisms of smoking. Compared to never smokers, current smokers had increased odds of HPV-16 infection by the antibody-mediated indirect effect (odds ratio [OR] = 1.29; 95% confidence interval [CI]: 1.11, 1.73); the estimated direct effect was very imprecise (OR = 0.57; 95% CI, 0.26-1.13). We observed a stronger estimated indirect effect among women who smoked at least half a pack of cigarettes daily (OR = 1.61, 95% CI, 1.27-2.15) than among women who smoked less than that threshold (OR = 1.09; 95% CI, 0.94-1.44). This is the first study to directly test the mechanism underlying smoking as an HPV cofactor. The results support current smoking as a risk factor earlier in the natural history of HPV and are consistent with the hypothesis that smoking increases the risk of a subsequent infection by reducing immunity. Published by Elsevier Inc.

Cannabis use and mania symptoms: a systematic review and meta-analysis.

PubMed

Gibbs, Melanie; Winsper, Catherine; Marwaha, Steven; Gilbert, Eleanor; Broome, Matthew; Singh, Swaran P

2015-01-15

Whilst cannabis use appears to be a causal risk factor for the development of schizophrenia-related psychosis, associations with mania remain relatively unknown. This review aimed to examine the impact of cannabis use on the incidence of manic symptoms and on their occurrence in those with pre-existing bipolar disorder. A systematic review of the scientific literature using the PRISMA guidelines. PsychINFO, Cochrane, Scopus, Embase and MEDLINE databases were searched for prospective studies. Six articles met inclusion criteria. These sampled 2391 individuals who had experienced mania symptoms. The mean length of follow up was 3.9 years. Studies support an association between cannabis use and the exacerbation of manic symptoms in those with previously diagnosed bipolar disorder. Furthermore, a meta-analysis of two studies suggests that cannabis use is associated with an approximately 3-fold (Odds Ratio: 2.97; 95% CI: 1.80-4.90) increased risk for the new onset of manic symptoms. We were only able to identify a small number of studies of variable quality, thus our conclusions remain preliminary. Our findings whilst tentative, suggest that cannabis use may worsen the occurrence of manic symptoms in those diagnosed with bipolar disorder, and may also act as a causal risk factor in the incidence of manic symptoms. This underscores the importance of discouraging cannabis use among youth and those with bipolar disorder to help prevent chronic psychiatric morbidity. More high quality prospective studies are required to fully elucidate how cannabis use may contribute to the development of mania over time. Copyright © 2014 Elsevier B.V. All rights reserved.

Determinants of work injuries in mines - an application of structural equation modelling.

PubMed

Maiti, J; Chatterjee, S; Bangdiwala, S I

2004-03-01

In spite of stringent regulations and much attention towards reducing risks in the physical environment, the mining industry continues to be associated with high levels of accidents, injuries and illnesses. Only engineering solutions to accident prevention are inappropriate unless coupled with focused attention to the attitudes and behaviours of the mineworkers in coping with the inherent physical, technical and situational risks. The present study identified these various risk factors and analysed their influences on work injury in a causal framework. Data were collected from an underground coalmine of India. The pattern and strength of relationships of 16 causal factors with work injuries were assessed through structural equation modelling. The case study results showed that negatively personified individuals are of major concern for safety improvement in the mine studied. They not only fail to avoid work injuries, they are unable to extend safe work behaviours in their work. The variable safety environment is negatively affected by personality, whereas social support has a positive relationship with safety environment. The variable job hazards appeared to have a significant relationship with job involvement, which has a negative relationship with work injury. Elimination of negative behaviours must be focused and committed by the mine safety management. Long term planning through (i) identification of negative individuals, (ii) proper councelling of adverse effects of negative behaviours, and (iii) special training with psychological treatment is highly required. Identification may begin while recruiting new workers through interview. Proper allocation of jobs (right person for right job) may be a judicial solution to this end.

Overcoming confirmation bias in causal attribution: a case study of antibiotic resistance risks.

PubMed

Cox, Louis Anthony Tony; Popken, Douglas A

2008-10-01

When they do not use formal quantitative risk assessment methods, many scientists (like other people) make mistakes and exhibit biases in reasoning about causation, if-then relations, and evidence. Decision-related conclusions or causal explanations are reached prematurely based on narrative plausibility rather than adequate factual evidence. Then, confirming evidence is sought and emphasized, but disconfirming evidence is ignored or discounted. This tendency has serious implications for health-related public policy discussions and decisions. We provide examples occurring in antimicrobial health risk assessments, including a case study of a recently reported positive relation between virginiamycin (VM) use in poultry and risk of resistance to VM-like (streptogramin) antibiotics in humans. This finding has been used to argue that poultry consumption causes increased resistance risks, that serious health impacts may result, and therefore use of VM in poultry should be restricted. However, the original study compared healthy vegetarians to hospitalized poultry consumers. Our examination of the same data using conditional independence tests for potential causality reveals that poultry consumption acted as a surrogate for hospitalization in this study. After accounting for current hospitalization status, no evidence remains supporting a causal relationship between poultry consumption and increased streptogramin resistance. This example emphasizes both the importance and the practical possibility of analyzing and presenting quantitative risk information using data analysis techniques (such as Bayesian model averaging (BMA) and conditional independence tests) that are as free as possible from potential selection, confirmation, and modeling biases.

The causal role of smoking on the risk of headache. A Mendelian randomization analysis in the HUNT Study.

PubMed

Johnsen, Marianne Bakke; Winsvold, Bendik Slagsvold; Børte, Sigrid; Vie, Gunnhild Åberge; Pedersen, Linda Margareth; Storheim, Kjersti; Skorpen, Frank; Hagen, Knut; Bjørngaard, Johan Håkon; Åsvold, Bjørn Olav; Zwart, John Anker

2018-05-10

Headache has been associated with various lifestyle- and psychosocial factors, one of which is smoking. The aim of the present study was to investigate whether the association between smoking intensity and headache is likely to be causal. 58 316 participants from the Nord-Trøndelag Health Study (HUNT) with information on headache status were genotyped for the rs1051730 C>T single-nucleotide polymorphism (SNP). The SNP was used as an instrument for smoking intensity in a Mendelian randomization (MR) analysis. Association between rs1051730 T alleles and headache was estimated by odds ratios (OR) with 95% confidence intervals (CI). Additionally, we investigated the association between the SNP and migraine or non-migrainous headache vs. no headache. All analyses were adjusted for age and sex. There was no strong evidence that the rs1051730 T allele was associated with headache in ever smokers (OR 0.99, 95% CI 0.95-1.02). Similarly, there was no association between the rs1051730 T allele and migraine or non-migrainous headache vs. no headache. Findings from this study do not support that there is a strong causal relationship between smoking intensity and any type of headache. Larger MR studies are required to examine whether higher smoking quantity can lead to a moderate increase in the risk of headache subtypes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Quantifying the improvement in sepsis diagnosis, documentation, and coding: the marginal causal effect of year of hospitalization on sepsis diagnosis.

PubMed

Jafarzadeh, S Reza; Thomas, Benjamin S; Marschall, Jonas; Fraser, Victoria J; Gill, Jeff; Warren, David K

2016-01-01

To quantify the coinciding improvement in the clinical diagnosis of sepsis, its documentation in the electronic health records, and subsequent medical coding of sepsis for billing purposes in recent years. We examined 98,267 hospitalizations in 66,208 patients who met systemic inflammatory response syndrome criteria at a tertiary care center from 2008 to 2012. We used g-computation to estimate the causal effect of the year of hospitalization on receiving an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis code for sepsis by estimating changes in the probability of getting diagnosed and coded for sepsis during the study period. When adjusted for demographics, Charlson-Deyo comorbidity index, blood culture frequency per hospitalization, and intensive care unit admission, the causal risk difference for receiving a discharge code for sepsis per 100 hospitalizations with systemic inflammatory response syndrome, had the hospitalization occurred in 2012, was estimated to be 3.9% (95% confidence interval [CI], 3.8%-4.0%), 3.4% (95% CI, 3.3%-3.5%), 2.2% (95% CI, 2.1%-2.3%), and 0.9% (95% CI, 0.8%-1.1%) from 2008 to 2011, respectively. Patients with similar characteristics and risk factors had a higher of probability of getting diagnosed, documented, and coded for sepsis in 2012 than in previous years, which contributed to an apparent increase in sepsis incidence. Copyright © 2016 Elsevier Inc. All rights reserved.

Education and myopia: assessing the direction of causality by mendelian randomisation.

PubMed

Mountjoy, Edward; Davies, Neil M; Plotnikov, Denis; Smith, George Davey; Rodriguez, Santiago; Williams, Cathy E; Guggenheim, Jeremy A; Atan, Denize

2018-06-06

To determine whether more years spent in education is a causal risk factor for myopia, or whether myopia is a causal risk factor for more years in education. Bidirectional, two sample mendelian randomisation study. Publically available genetic data from two consortiums applied to a large, independent population cohort. Genetic variants used as proxies for myopia and years of education were derived from two large genome wide association studies: 23andMe and Social Science Genetic Association Consortium (SSGAC), respectively. 67 798 men and women from England, Scotland, and Wales in the UK Biobank cohort with available information for years of completed education and refractive error. Mendelian randomisation analyses were performed in two directions: the first exposure was the genetic predisposition to myopia, measured with 44 genetic variants strongly associated with myopia in 23andMe, and the outcome was years in education; and the second exposure was the genetic predisposition to higher levels of education, measured with 69 genetic variants from SSGAC, and the outcome was refractive error. Conventional regression analyses of the observational data suggested that every additional year of education was associated with a more myopic refractive error of -0.18 dioptres/y (95% confidence interval -0.19 to -0.17; P<2e-16). Mendelian randomisation analyses suggested the true causal effect was even stronger: -0.27 dioptres/y (-0.37 to -0.17; P=4e-8). By contrast, there was little evidence to suggest myopia affected education (years in education per dioptre of refractive error -0.008 y/dioptre, 95% confidence interval -0.041 to 0.025, P=0.6). Thus, the cumulative effect of more years in education on refractive error means that a university graduate from the United Kingdom with 17 years of education would, on average, be at least -1 dioptre more myopic than someone who left school at age 16 (with 12 years of education). Myopia of this magnitude would be sufficient to necessitate the use of glasses for driving. Sensitivity analyses showed minimal evidence for genetic confounding that could have biased the causal effect estimates. This study shows that exposure to more years in education contributes to the rising prevalence of myopia. Increasing the length of time spent in education may inadvertently increase the prevalence of myopia and potential future visual disability. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Education and myopia: assessing the direction of causality by mendelian randomisation

PubMed Central

Mountjoy, Edward; Davies, Neil M; Plotnikov, Denis; Smith, George Davey; Rodriguez, Santiago; Williams, Cathy E; Guggenheim, Jeremy A

2018-01-01

Abstract Objectives To determine whether more years spent in education is a causal risk factor for myopia, or whether myopia is a causal risk factor for more years in education. Design Bidirectional, two sample mendelian randomisation study. Setting Publically available genetic data from two consortiums applied to a large, independent population cohort. Genetic variants used as proxies for myopia and years of education were derived from two large genome wide association studies: 23andMe and Social Science Genetic Association Consortium (SSGAC), respectively. Participants 67 798 men and women from England, Scotland, and Wales in the UK Biobank cohort with available information for years of completed education and refractive error. Main outcome measures Mendelian randomisation analyses were performed in two directions: the first exposure was the genetic predisposition to myopia, measured with 44 genetic variants strongly associated with myopia in 23andMe, and the outcome was years in education; and the second exposure was the genetic predisposition to higher levels of education, measured with 69 genetic variants from SSGAC, and the outcome was refractive error. Results Conventional regression analyses of the observational data suggested that every additional year of education was associated with a more myopic refractive error of −0.18 dioptres/y (95% confidence interval −0.19 to −0.17; P<2e-16). Mendelian randomisation analyses suggested the true causal effect was even stronger: −0.27 dioptres/y (−0.37 to −0.17; P=4e-8). By contrast, there was little evidence to suggest myopia affected education (years in education per dioptre of refractive error −0.008 y/dioptre, 95% confidence interval −0.041 to 0.025, P=0.6). Thus, the cumulative effect of more years in education on refractive error means that a university graduate from the United Kingdom with 17 years of education would, on average, be at least −1 dioptre more myopic than someone who left school at age 16 (with 12 years of education). Myopia of this magnitude would be sufficient to necessitate the use of glasses for driving. Sensitivity analyses showed minimal evidence for genetic confounding that could have biased the causal effect estimates. Conclusions This study shows that exposure to more years in education contributes to the rising prevalence of myopia. Increasing the length of time spent in education may inadvertently increase the prevalence of myopia and potential future visual disability. PMID:29875094

When Work is Related to Disease, What Establishes Evidence for a Causal Relation?

PubMed

Verbeek, Jos

2012-06-01

Establishing a causal relationship between factors at work and disease is difficult for occupational physicians and researchers. This paper seeks to provide arguments for the judgement of evidence of causality in observational studies that relate work factors to disease. I derived criteria for the judgement of evidence of causality from the following sources: the criteria list of Hill, the approach by Rothman, the methods used by International Agency for Research on Cancer (IARC), and methods used by epidemiologists. The criteria are applied to two cases of putative occupational diseases; breast cancer caused by shift work and aerotoxic syndrome. Only three of the Hill criteria can be applied to an actual study. Rothman stresses the importance of confounding and alternative explanations than the putative cause. IARC closely follows Hill, but they also incorporate other than epidemiological evidence. Applied to shift work and breast cancer, these results have found moderate evidence for a causal relationship, but applied to the aerotoxic syndrome, there is an absence of evidence of causality. There are no ready to use algorithms for judgement of evidence of causality. Criteria from different sources lead to similar results and can make a conclusion of causality more or less likely.

When Work is Related to Disease, What Establishes Evidence for a Causal Relation?

PubMed Central

2012-01-01

Establishing a causal relationship between factors at work and disease is difficult for occupational physicians and researchers. This paper seeks to provide arguments for the judgement of evidence of causality in observational studies that relate work factors to disease. I derived criteria for the judgement of evidence of causality from the following sources: the criteria list of Hill, the approach by Rothman, the methods used by International Agency for Research on Cancer (IARC), and methods used by epidemiologists. The criteria are applied to two cases of putative occupational diseases; breast cancer caused by shift work and aerotoxic syndrome. Only three of the Hill criteria can be applied to an actual study. Rothman stresses the importance of confounding and alternative explanations than the putative cause. IARC closely follows Hill, but they also incorporate other than epidemiological evidence. Applied to shift work and breast cancer, these results have found moderate evidence for a causal relationship, but applied to the aerotoxic syndrome, there is an absence of evidence of causality. There are no ready to use algorithms for judgement of evidence of causality. Criteria from different sources lead to similar results and can make a conclusion of causality more or less likely. PMID:22993715

Heterogeneous rates for birth defects in Latin America: hints on causality.

PubMed

Lopez-Camelo, J S; Orioli, I M

1996-01-01

The aim of this work was to disclose risk factors associated with birth defects which were heterogeneously distributed in the different geographic regions sampled by the Latin American Collaborative Study of Congenital Malformations (ECLAMC). The material included 2,159,065 hospital births, delivered in the 1967-1989 period in 24 geographic regions of Latin America. Birth defect types with 50 case-control pairs or more were analyzed. A risk factor was defined as that available variable with differential geographic rates, correlated with those of a given birth defect type. Identified factors were tested by case-control multivariate logistic regression to confirm their role in the occurrence of the defect. Altitude and maternal acute illness during first trimester of pregnancy, named influenza, were risk factors for microtia. Prenatal drug exposure, mainly sex hormones, were connected with the occurrence of hypospadias in low frequency areas, while Native ancestry was a "protective" factor in the same regions. Acute (influenza), and chronic (epilepsy and syphilis) maternal illness during first trimester of pregnancy and gravidity higher than four were risk factors for cleft lip. The independence of these variables from maternal age suggested that low maternal socioeconomic level could explain the high birth defect order and, perhaps, syphilis in mothers. Postaxial polydactyly was associated with parental consanguinity, as well as Afro-American ancestry, suggesting genetic heterogeneity.

Reported gum disease as a cardiovascular risk factor in adults with intellectual disabilities.

PubMed

Hsieh, K; Murthy, S; Heller, T; Rimmer, J H; Yen, G

2018-03-01

Several risk factors for cardiovascular disease (CVD) have been identified among adults with intellectual disabilities (ID). Periodontitis has been reported to increase the risk of developing a CVD in the general population. Given that individuals with ID have been reported to have a higher prevalence of poor oral health than the general population, the purpose of this study was to determine whether adults with ID with informant reported gum disease present greater reported CVD than those who do not have reported gum disease and whether gum disease can be considered a risk factor for CVD. Using baseline data from the Longitudinal Health and Intellectual Disability Study from which informant survey data were collected, 128 participants with reported gum disease and 1252 subjects without reported gum disease were identified. A series of univariate logistic regressions was conducted to identify potential confounding factors for a multiple logistic regression. The series of univariate logistic regressions identified age, Down syndrome, hypercholesterolemia, hypertension, reported gum disease, daily consumption of fruits and vegetables and the addition of table salt as significant risk factors for reported CVD. When the significant factors from the univariate logistic regression were included in the multiple logistic analysis, reported gum disease remained as an independent risk factor for reported CVD after adjusting for the remaining risk factors. Compared with the adults with ID without reported gum disease, adults in the gum disease group demonstrated a significantly higher prevalence of reported CVD (19.5% vs. 9.7%; P = .001). After controlling for other risk factors, reported gum disease among adults with ID may be associated with a higher risk of CVD. However, further research that also includes clinical indices of periodontal disease and CVD for this population is needed to determine if there is a causal relationship between gum disease and CVD. © 2017 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Cardiovascular risk factors and TIA characteristics in 19,872 Swedish TIA patients.

PubMed

Ström, J O; Tavosian, A; Appelros, P

2016-12-01

Transient ischemic attack (TIA) constitutes a major risk factor for stroke, making TIA patients an important group for secondary intervention. The aim of this study was to account for risk factor prevalence in TIA patients and analyze the association between TIA characteristics and risk factors. We included 20,871 TIA events in 19,872 patients who were registered in the Swedish Riksstroke registry during the years 2010 through 2012. Data from other Swedish registers were used for comparison. The following variables were analyzed: age, sex, diabetes mellitus, atrial fibrillation (AF), cigarette smoking, and antihypertensive treatment. Compared to the general population (based on data retrieved from Sweden's national public health survey 'Health on equal terms'), TIA patients more often had diabetes mellitus (prevalence ratio, PR = 2.3), AF without oral anticoagulants (OAC) (PR = 2.8), and AF on OAC (PR = 1.6). Blood pressure medication was less prevalent among TIA patients than in the general population (PR = 0.57). Increasing age was associated with longer attacks. The fact that diabetes mellitus, atrial fibrillation, and smoking are more common in TIA patients than in the general population suggests that these factors are risk factors for TIA, even if causal relations cannot be proven. The relation between increasing age and longer attacks possibly reflects an increased proportion of embolic TIAs, or impaired recovery ability. Our results also suggest a significant proportion of untreated hypertension cases in the population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Gene-environment interplay in the etiology of psychosis.

PubMed

Zwicker, Alyson; Denovan-Wright, Eileen M; Uher, Rudolf

2018-01-15

Schizophrenia and other types of psychosis incur suffering, high health care costs and loss of human potential, due to the combination of early onset and poor response to treatment. Our ability to prevent or cure psychosis depends on knowledge of causal mechanisms. Molecular genetic studies show that thousands of common and rare variants contribute to the genetic risk for psychosis. Epidemiological studies have identified many environmental factors associated with increased risk of psychosis. However, no single genetic or environmental factor is sufficient to cause psychosis on its own. The risk of developing psychosis increases with the accumulation of many genetic risk variants and exposures to multiple adverse environmental factors. Additionally, the impact of environmental exposures likely depends on genetic factors, through gene-environment interactions. Only a few specific gene-environment combinations that lead to increased risk of psychosis have been identified to date. An example of replicable gene-environment interaction is a common polymorphism in the AKT1 gene that makes its carriers sensitive to developing psychosis with regular cannabis use. A synthesis of results from twin studies, molecular genetics, and epidemiological research outlines the many genetic and environmental factors contributing to psychosis. The interplay between these factors needs to be considered to draw a complete picture of etiology. To reach a more complete explanation of psychosis that can inform preventive strategies, future research should focus on longitudinal assessments of multiple environmental exposures within large, genotyped cohorts beginning early in life.

Intelligent diagnosis of jaundice with dynamic uncertain causality graph model.

PubMed

Hao, Shao-Rui; Geng, Shi-Chao; Fan, Lin-Xiao; Chen, Jia-Jia; Zhang, Qin; Li, Lan-Juan

2017-05-01

Jaundice is a common and complex clinical symptom potentially occurring in hepatology, general surgery, pediatrics, infectious diseases, gynecology, and obstetrics, and it is fairly difficult to distinguish the cause of jaundice in clinical practice, especially for general practitioners in less developed regions. With collaboration between physicians and artificial intelligence engineers, a comprehensive knowledge base relevant to jaundice was created based on demographic information, symptoms, physical signs, laboratory tests, imaging diagnosis, medical histories, and risk factors. Then a diagnostic modeling and reasoning system using the dynamic uncertain causality graph was proposed. A modularized modeling scheme was presented to reduce the complexity of model construction, providing multiple perspectives and arbitrary granularity for disease causality representations. A "chaining" inference algorithm and weighted logic operation mechanism were employed to guarantee the exactness and efficiency of diagnostic reasoning under situations of incomplete and uncertain information. Moreover, the causal interactions among diseases and symptoms intuitively demonstrated the reasoning process in a graphical manner. Verification was performed using 203 randomly pooled clinical cases, and the accuracy was 99.01% and 84.73%, respectively, with or without laboratory tests in the model. The solutions were more explicable and convincing than common methods such as Bayesian Networks, further increasing the objectivity of clinical decision-making. The promising results indicated that our model could be potentially used in intelligent diagnosis and help decrease public health expenditure.

Intelligent diagnosis of jaundice with dynamic uncertain causality graph model*

PubMed Central

Hao, Shao-rui; Geng, Shi-chao; Fan, Lin-xiao; Chen, Jia-jia; Zhang, Qin; Li, Lan-juan

2017-01-01

Jaundice is a common and complex clinical symptom potentially occurring in hepatology, general surgery, pediatrics, infectious diseases, gynecology, and obstetrics, and it is fairly difficult to distinguish the cause of jaundice in clinical practice, especially for general practitioners in less developed regions. With collaboration between physicians and artificial intelligence engineers, a comprehensive knowledge base relevant to jaundice was created based on demographic information, symptoms, physical signs, laboratory tests, imaging diagnosis, medical histories, and risk factors. Then a diagnostic modeling and reasoning system using the dynamic uncertain causality graph was proposed. A modularized modeling scheme was presented to reduce the complexity of model construction, providing multiple perspectives and arbitrary granularity for disease causality representations. A “chaining” inference algorithm and weighted logic operation mechanism were employed to guarantee the exactness and efficiency of diagnostic reasoning under situations of incomplete and uncertain information. Moreover, the causal interactions among diseases and symptoms intuitively demonstrated the reasoning process in a graphical manner. Verification was performed using 203 randomly pooled clinical cases, and the accuracy was 99.01% and 84.73%, respectively, with or without laboratory tests in the model. The solutions were more explicable and convincing than common methods such as Bayesian Networks, further increasing the objectivity of clinical decision-making. The promising results indicated that our model could be potentially used in intelligent diagnosis and help decrease public health expenditure. PMID:28471111

Instrumental Variable Analysis with a Nonlinear Exposure–Outcome Relationship

PubMed Central

Davies, Neil M.; Thompson, Simon G.

2014-01-01

Background: Instrumental variable methods can estimate the causal effect of an exposure on an outcome using observational data. Many instrumental variable methods assume that the exposure–outcome relation is linear, but in practice this assumption is often in doubt, or perhaps the shape of the relation is a target for investigation. We investigate this issue in the context of Mendelian randomization, the use of genetic variants as instrumental variables. Methods: Using simulations, we demonstrate the performance of a simple linear instrumental variable method when the true shape of the exposure–outcome relation is not linear. We also present a novel method for estimating the effect of the exposure on the outcome within strata of the exposure distribution. This enables the estimation of localized average causal effects within quantile groups of the exposure or as a continuous function of the exposure using a sliding window approach. Results: Our simulations suggest that linear instrumental variable estimates approximate a population-averaged causal effect. This is the average difference in the outcome if the exposure for every individual in the population is increased by a fixed amount. Estimates of localized average causal effects reveal the shape of the exposure–outcome relation for a variety of models. These methods are used to investigate the relations between body mass index and a range of cardiovascular risk factors. Conclusions: Nonlinear exposure–outcome relations should not be a barrier to instrumental variable analyses. When the exposure–outcome relation is not linear, either a population-averaged causal effect or the shape of the exposure–outcome relation can be estimated. PMID:25166881

Beyond Correlates: A Review of Risk and Protective Factors for Adolescent Dating Violence Perpetration

PubMed Central

Vagi, Kevin J.; Rothman, Emily; Latzman, Natasha E.; Tharp, Andra Teten; Hall, Diane M.; Breiding, Matthew J.

2013-01-01

Dating violence is a serious public health problem. In recent years, the U.S. Centers for Disease Control and Prevention (CDC) and other entities have made funding available to community based agencies for dating violence prevention. Practitioners who are tasked with developing dating violence prevention strategies should pay particular attention to risk and protective factors for dating violence perpetration that have been established in longitudinal studies. This has been challenging to date because the scientific literature on the etiology of dating violence is somewhat limited, and because there have been no comprehensive reviews of the literature that clearly distinguish correlates of dating violence perpetration from risk or protective factors that have been established through longitudinal research. This is problematic because prevention programs may then target factors that are merely correlated with dating violence perpetration, and have no causal influence, which could potentially limit the effectiveness of the programs. In this article, we review the literature on risk and protective factors for adolescent dating violence perpetration and highlight those factors for which temporal precedence has been established by one or more studies. This review is intended as a guide for researchers and practitioners as they formulate prevention programs. We reviewed articles published between 2000–2010 that reported on adolescent dating violence perpetration using samples from the United States or Canada. In total, 53 risk factors and six protective factors were identified from 20 studies. Next steps for etiological research in adolescent dating violence are discussed, as well as future directions for prevention program developers. PMID:23385616

Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others.

PubMed

Seppala, Lotta J; van de Glind, Esther M M; Daams, Joost G; Ploegmakers, Kimberley J; de Vries, Max; Wermelink, Anne M A T; van der Velde, Nathalie

2018-04-01

The use of psychotropic medication and cardiovascular medication has been associated with an increased risk of falling. However, other frequently prescribed medication classes are still under debate as potential risk factors for falls in the older population. The aim of this systematic review and meta-analysis is to evaluate the associations between fall risk and nonpsychotropic and noncardiovascular medications. A systematic review and meta-analysis. A search was conducted in Medline, PsycINFO, and Embase. Key search concepts were "falls," "aged," "medication," and "causality." Studies were included that investigated nonpsychotropic and noncardiovascular medications as risk factors for falls in participants ≥60 years or participants with a mean age ≥70 years. A meta-analysis was performed using the generic inverse variance method, pooling unadjusted and adjusted odds ratio (OR) estimates separately. In a qualitative synthesis, 281 studies were included. The results of meta-analysis using adjusted data were as follows (a pooled OR [95% confidence interval]): analgesics, 1.42 (0.91-2.23); nonsteroidal anti-inflammatory drugs (NSAIDs), 1.09 (0.96-1.23); opioids, 1.60 (1.35-1.91); anti-Parkinson drugs, 1.54 (0.99-2.39); antiepileptics, 1.55 (1.25-1.92); and polypharmacy, 1.75 (1.27-2.41). Most of the meta-analyses resulted in substantial heterogeneity that did not disappear after stratification for population and setting in most cases. In a descriptive synthesis, consistent associations with falls were observed for long-term proton pump inhibitor use and opioid initiation. Laxatives showed inconsistent associations with falls (7/20 studies showing a positive association). Opioid and antiepileptic use and polypharmacy were significantly associated with increased risk of falling in the meta-analyses. Long-term use of proton pump inhibitors and opioid initiation might increase the fall risk. Future research is necessary because the causal role of some medication classes as fall-risk-increasing drugs remains unclear, and the existing literature contains significant limitations. Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

How are multifactorial beliefs about the role of genetics and behavior in cancer causation associated with cancer risk cognitions and emotions in the US population?

PubMed

Hamilton, Jada G; Waters, Erika A

2018-02-01

People who believe that cancer has both genetic and behavioral risk factors have more accurate mental models of cancer causation and may be more likely to engage in cancer screening behaviors than people who do not hold such multifactorial causal beliefs. This research explored possible health cognitions and emotions that might produce such differences. Using nationally representative cross-sectional data from the US Health Information National Trends Survey (N = 2719), we examined whether endorsing a multifactorial model of cancer causation was associated with perceptions of risk and other cancer-related cognitions and affect. Data were analyzed using linear regression with jackknife variance estimation and procedures to account for the complex survey design and weightings. Bivariate and multivariable analyses indicated that people who endorsed multifactorial beliefs about cancer had higher absolute risk perceptions, lower pessimism about cancer prevention, and higher worry about harm from environmental toxins that could be ingested or that emanate from consumer products (Ps < .05). Bivariate analyses indicated that multifactorial beliefs were also associated with higher feelings of risk, but multivariable analyses suggested that this effect was accounted for by the negative affect associated with reporting a family history of cancer. Multifactorial beliefs were not associated with believing that everything causes cancer or that there are too many cancer recommendations to follow (Ps > .05). Holding multifactorial causal beliefs about cancer are associated with a constellation of risk perceptions, health cognitions, and affect that may motivate cancer prevention and detection behavior. Copyright © 2017 John Wiley & Sons, Ltd.

What Women Think: Cancer Causal Attributions in a Diverse Sample of Women

PubMed Central

Rodríguez, Vivian M.; Gyure, Maria E.; Corona, Rosalie; Bodurtha, Joann N.; Bowen, Deborah J.; Quillin, John M.

2014-01-01

Women hold diverse beliefs about cancer etiology, potentially affecting their use of cancer preventive behaviors. To date, research has greatly focused on the causal attributions cancer patients and survivors hold about cancer, and studies have been conducted primarily with White participants. Less is known about causal attributions held by women with and without a family history of cancer from a diverse community sample. This study sought to identify cancer causal attributions of women with and without a family history of cancer, and explore its relation to socio-cultural factors. Diverse women (60% African-American) recruited at an urban, safety-net women's health clinic (N=471) reported factors they believed cause cancer. Responses were coded into nine attributions and analyzed using chi-squares and logistic regressions. Lifestyle-choices (63%), genetics/heredity (34%), and environmental-exposures (19%) were the top causal attributions identified. Women without a family history of cancer were more likely to identify genetics/heredity as an attribution for cancer than women with a history of cancer in their families. Women who identified as White, who had a higher educational attainment, and had commercial insurance were more likely to report genetics/heredity as a causal attribution for cancer. These findings suggest that socio-cultural factors may play a role in the causal attributions individuals make about cancer, which can, in turn, inform cancer awareness and prevention messages. PMID:25398057

Multivariate Granger causality: an estimation framework based on factorization of the spectral density matrix

PubMed Central

Wen, Xiaotong; Rangarajan, Govindan; Ding, Mingzhou

2013-01-01

Granger causality is increasingly being applied to multi-electrode neurophysiological and functional imaging data to characterize directional interactions between neurons and brain regions. For a multivariate dataset, one might be interested in different subsets of the recorded neurons or brain regions. According to the current estimation framework, for each subset, one conducts a separate autoregressive model fitting process, introducing the potential for unwanted variability and uncertainty. In this paper, we propose a multivariate framework for estimating Granger causality. It is based on spectral density matrix factorization and offers the advantage that the estimation of such a matrix needs to be done only once for the entire multivariate dataset. For any subset of recorded data, Granger causality can be calculated through factorizing the appropriate submatrix of the overall spectral density matrix. PMID:23858479

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium.

PubMed

Skaaby, Tea; Taylor, Amy E; Jacobsen, Rikke K; Paternoster, Lavinia; Thuesen, Betina H; Ahluwalia, Tarunveer S; Larsen, Sofus C; Zhou, Ang; Wong, Andrew; Gabrielsen, Maiken E; Bjørngaard, Johan H; Flexeder, Claudia; Männistö, Satu; Hardy, Rebecca; Kuh, Diana; Barry, Sarah J; Tang Møllehave, Line; Cerqueira, Charlotte; Friedrich, Nele; Bonten, Tobias N; Noordam, Raymond; Mook-Kanamori, Dennis O; Taube, Christian; Jessen, Leon E; McConnachie, Alex; Sattar, Naveed; Upton, Mark N; McSharry, Charles; Bønnelykke, Klaus; Bisgaard, Hans; Schulz, Holger; Strauch, Konstantin; Meitinger, Thomas; Peters, Annette; Grallert, Harald; Nohr, Ellen A; Kivimaki, Mika; Kumari, Meena; Völker, Uwe; Nauck, Matthias; Völzke, Henry; Power, Chris; Hyppönen, Elina; Hansen, Torben; Jørgensen, Torben; Pedersen, Oluf; Salomaa, Veikko; Grarup, Niels; Langhammer, Arnulf; Romundstad, Pål R; Skorpen, Frank; Kaprio, Jaakko; R Munafò, Marcus; Linneberg, Allan

2017-05-22

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

Risk factors associated with rural water supply failure: A 30-year retrospective study of handpumps on the south coast of Kenya.

PubMed

Foster, Tim; Willetts, Juliet; Lane, Mike; Thomson, Patrick; Katuva, Jacob; Hope, Rob

2018-06-01

An improved understanding of failure risks for water supplies in rural sub-Saharan Africa will be critical to achieving the global goal of safe water for all by 2030. In the absence of longitudinal biophysical and operational data, investigations into water point failure risk factors have to date been limited to cross-sectional research designs. This retrospective cohort study applies survival analysis to identify factors that predict failure risks for handpumps installed on boreholes along the south coast of Kenya from the 1980s. The analysis is based on a unique dataset linking attributes of >300 water points at the time of installation with their operational lifespan over the following decades. Cox proportional hazards and accelerated failure time models suggest water point failure risks are higher and lifespans are shorter when water supplied is more saline, static water level is deeper, and groundwater is pumped from an unconsolidated sand aquifer. The risk of failure also appears to grow as distance to spare part suppliers increases. To bolster the sustainability of rural water services and ensure no community is left behind, post-construction support mechanisms will need to mitigate heterogeneous environmental and geographical challenges. Further studies are needed to better understand the causal pathways that underlie these risk factors in order to inform policies and practices that ensure water services are sustained even where unfavourable conditions prevail. Copyright © 2018 Elsevier B.V. All rights reserved.

Risk and Protective Factors for Childhood Asthma: What Is the Evidence?

PubMed

Castro-Rodriguez, Jose A; Forno, Erick; Rodriguez-Martinez, Carlos E; Celedón, Juan C

To summarize the principal findings on risk and protective factors for childhood asthma, we retrieved systematic reviews on these topics in children (aged 1 to 18 years), up to January 2016, through MEDLINE, EMBASE, CINAHL, SCOPUS, and CDSR. A total of 227 studies were searched from databases. Among those, 41 systematic reviews (SRs) were included: 9 focused on prenatal factors, 5 on perinatal factors, and 27 on postnatal factors. Of these 41 SRs, 83% had good methodological quality, as determined by the Assess Systematic Reviews tool. After reviewing all evidence, parental asthma, prenatal environmental tobacco smoke, and prematurity (particularly very preterm birth) are well-established risk factors for childhood asthma. Current findings do suggest mild-to-moderate causal effects of certain modifiable behaviors or exposures during pregnancy (maternal weight gain or obesity, maternal use of antibiotics or paracetamol, and maternal stress), the perinatal period (birth by Caesarean delivery), or postnatal life (severe respiratory syncytial virus infection, overweight or obesity, indoor exposure to mold or fungi, and outdoor air pollution) on childhood asthma, but this suggestive evidence must be confirmed in interventional studies or (if interventions are not feasible) well-designed prospective studies. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Severe intimate partner physical violence as a risk factor for inadequate cervical cancer screening.

PubMed

Rafael, Ricardo de Mattos Russo; Moura, Anna Tereza Miranda Soares de

2017-12-18

With the aim of assessing the occurrence of severe intimate partner physical violence as a risk factor for inadequate screening of uterine cervical cancer, a case-control study was performed with a multidimensional questionnaire in a sample of 640 users of the Family Health Strategy in the Municipality of Nova Iguaçu, Rio de Janeiro State, Brazil. Cases were defined as women who had not had a cervical cytology test in the previous three years. The results showed that severe physical violence against the woman (adjustedOR = 2.2; 95%CI: 1.1-4.4) and co-occurrence of the event in the couple (adjustedOR = 3.8; 95%CI: 1.4-9.8) were risk factors for inadequate screening. Alcohol abuse by the woman was an effect modifier for not having the test among victims of violence (adjustedOR = 10.2; 95%CI: 1.8-56.4) and in cases of co-occurrence of violence (adjustedOR = 8.5; 95%CI: 1.4-50.7). In addition to known causal factors for intimate partner violence, the results point to a risk association between women's exposure to abuse and inadequate screening. The findings call for an expanded view of women's absenteeism from screening, since this indicator can represent unmet demands not readily detected by health teams.

Property transmission: an explanatory account of the role of similarity information in causal inference.

PubMed

White, Peter A

2009-09-01

Many kinds of common and easily observed causal relations exhibit property transmission, which is a tendency for the causal object to impose its own properties on the effect object. It is proposed that property transmission becomes a general and readily available hypothesis used to make interpretations and judgments about causal questions under conditions of uncertainty, in which property transmission functions as a heuristic. The property transmission hypothesis explains why and when similarity information is used in causal inference. It can account for magical contagion beliefs, some cases of illusory correlation, the correspondence bias, overestimation of cross-situational consistency in behavior, nonregressive tendencies in prediction, the belief that acts of will are causes of behavior, and a range of other phenomena. People learn that property transmission is often moderated by other factors, but under conditions of uncertainty in which the operation of relevant other factors is unknown, it tends to exhibit a pervasive influence on thinking about causality. (c) 2009 APA, all rights reserved.

Using genetics to test the causal relationship of total adiposity and periodontitis: Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium

PubMed Central

Shungin, Dmitry; Cornelis, Marilyn C; Divaris, Kimon; Holtfreter, Birte; Shaffer, John R; Yu, Yau-Hua; Barros, Silvana P; Beck, James D; Biffar, Reiner; Boerwinkle, Eric A; Crout, Richard J.; Ganna, Andrea; Hallmans, Goran; Hindy, George; Hu, Frank B; Kraft, Peter; McNeil, Daniel W; Melander, Olle; Moss, Kevin L; North, Kari E; Orho-Melander, Marju; Pedersen, Nancy L; Ridker, Paul M; Rimm, Eric B; Rose, Lynda M; Rukh, Gull; Teumer, Alexander; Weyant, Robert J; Chasman, Daniel I; Joshipura, Kaumudi; Kocher, Thomas; Magnusson, Patrik KE; Marazita, Mary L; Nilsson, Peter; Offenbacher, Steve; Davey Smith, George; Lundberg, Pernilla; Palmer, Tom M; Timpson, Nicholas J; Johansson, Ingegerd; Franks, Paul W

2015-01-01

Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49 066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17 672/31 394 with/without periodontitis); 68 761 participants with BMI and genotype data; and 57 871 participants (18 881/38 990 with/without periodontitis) with data on BMI and periodontitis. Results: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI:1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. Conclusions: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals. PMID:26050256

Psychosocial work factors, major depressive and generalised anxiety disorders: results from the French national SIP study.

PubMed

Murcia, Marie; Chastang, Jean-François; Niedhammer, Isabelle

2013-04-25

Anxiety and depression are prevalent mental disorders in working populations. The risk factors of these disorders are not completely well known. Developing knowledge on occupational risk factors for mental disorders appears crucial. This study investigates the association between various classical and emergent psychosocial work factors and major depressive and generalised anxiety disorders in the French working population. The study was based on a national random sample of 3765 men and 3944 women of the French working population (SIP 2006 survey). Major Depressive Disorder (MDD) and Generalised Anxiety Disorder (GAD) were measured using a standardised diagnostic interview (MINI). Occupational factors included psychosocial work factors as well as biomechanical, physical, and chemical exposures. Adjustment variables included age, occupation, marital status, social support, and life events. Multivariate analysis was performed using logistic regression analysis. Low decision latitude, overcommitment, and emotional demands were found to be risk factors for both MDD-GAD among both genders. Other risk factors were observed: high psychological demands, low reward, ethical conflict, and job insecurity, but differences were found according to gender and outcome. Significant interaction terms were observed suggesting that low decision latitude, high psychological demands, and job insecurity had stronger effects on mental disorders for men than for women. Given the cross-sectional study design, no causal conclusion could be drawn. This study showed significant associations between classical and emergent psychosocial work factors and MDD-GAD. Preventive actions targeting various psychosocial work factors, including emergent factors, may help to reduce mental disorders at the workplace. Copyright © 2012 Elsevier B.V. All rights reserved.

Pathways to psychosis in cannabis abuse.

PubMed

Shrivastava, Amresh; Johnston, Megan; Terpstra, Kristen; Bureau, Yves

2015-04-01

Cannabis has been implicated as a risk factor for the development of schizophrenia, but the exact biological mechanisms remain unclear. In this review, we attempt to understand the neurobiological pathways that link cannabis use to schizophrenia. This has been an area of great debate; despite similarities between cannabis users and schizophrenia patients, the evidence is not sufficient to establish cause-and-effect. There have been advances in the understanding of the mechanisms of cannabis dependence as well as the role of the cannabinoid system in the development of psychosis and schizophrenia. The neurobiological mechanisms associated with the development of psychosis and effects from cannabis use may be similar but remain elusive. In order to better understand these associations, this paper will show common neurobiological and neuroanatomical changes as well as common cognitive dysfunction in cannabis users and patients of schizophrenia. We conclude that epidemiologic evidence highlights potential causal links; however, neurobiological evidence for causality remains weak.

Does health affect portfolio choice?

PubMed

Love, David A; Smith, Paul A

2010-12-01

A number of recent studies find that poor health is empirically associated with a safer portfolio allocation. It is difficult to say, however, whether this relationship is truly causal. Both health status and portfolio choice are influenced by unobserved characteristics such as risk attitudes, impatience, information, and motivation, and these unobserved factors, if not adequately controlled for, can induce significant bias in the estimates of asset demand equations. Using the 1992-2006 waves of the Health and Retirement Study, we investigate how much of the connection between health and portfolio choice is causal and how much is due to the effects of unobserved heterogeneity. Accounting for unobserved heterogeneity with fixed effects and correlated random effects models, we find that health does not appear to significantly affect portfolio choice among single households. For married households, we find a small effect (about 2-3 percentage points) from being in the lowest of five self-reported health categories. Copyright © 2009 John Wiley & Sons, Ltd.

The Conundrum of Causality in Tumor Virology: The Cases of KSHV and MCV

PubMed Central

Moore, Patrick S.; Chang, Yuan

2014-01-01

Controversy has plagued tumor virology since the first tumor viruses were described over 100 years ago. Methods to establish cancer causation, such as Koch’s postulates, work poorly or not at all for these viruses. Kaposi’s sarcoma herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using nucleic acid identification methods but they represent opposite poles in the patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk factors that contribute to infection and subsequent cancers. MCV and Merkel cell carcinoma (MCC), in contrast, is an example in which mutations to our normal viral flora contribute to cancer. Given the near-ubiquity of human MCV infection, establishing cancer causality relies on molecular evidence that does not fit comfortably within traditional infectious disease epidemiological models. These two viruses reveal some of the challenges and opportunities for inferring viral cancer causation in the age of molecular biology. PMID:24304907

Risk perception is not associated with attendance at a preventive intervention for type 2 diabetes mellitus among South Asians at risk of diabetes.

PubMed

Vlaar, Everlina M A; Nierkens, Vera; Nicolaou, Mary; Middelkoop, Barend J C; Stronks, Karien; van Valkengoed, Irene G M

2015-04-01

To evaluate the association between risk perception and attendance in a diabetes prevention programme among South Asians with a high risk for diabetes. An observational study. We measured risk perception during the baseline interview with causal beliefs, perceived susceptibility and perceived controllability. We used logistic regression to examine the relationship between risk perception and attendance. We adjusted for relevant sociodemographic factors, screening results and psychosocial factors. The Hague, the Netherlands. Five hundred and thirty-five Hindustani Surinamese (South Asians) aged 18-60 years from a lifestyle-versus-control intervention for the prevention of diabetes. In total, 68·2% attended the lifestyle or control intervention. Participants perceived lifestyle and heredity to increase the risk of diabetes and perceived increasing physical activity to decrease it. Only 44·2% of the participants perceived themselves as susceptible to diabetes and only those who perceived a family history of diabetes as a cause of diabetes appeared to be more inclined to attend. However, after adjustment for confounding, the association was not statistically significant. Risk perception was not significantly associated with attendance. The results suggest that increasing the risk perception alone in this South Asian population is unlikely to increase the attendance at a diabetes prevention programme.

The association between human papillomavirus and oropharyngeal squamous cell Carcinoma: Reviewed according to the Bradford Hill criteria for causality.

PubMed

Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe; Lajer, Christel Bræmer

2016-12-01

There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils. The association is geographically consistent throughout the economically developed world. The presence and integration of high-risk human papillomavirus genome in tonsillar tumours, and expression of viral oncogenes, are specific and plausible. Analogous to human papillomavirus in cervical cancer, the rising incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident. Copyright © 2016 Elsevier Ltd. All rights reserved.

Carnitine Palmitoyltransferase 1A P479L and Infant Death: Policy Implications of Emerging Data

PubMed Central

Fohner, Alison E.; Garrison, Nanibaa’ A.; Austin, Melissa A.; Burke, Wylie

2017-01-01

Carnitine Palmitoyltransferase 1 Isoform A (CPT1A) is a crucial enzyme for the transport of long chain fatty acids into the mitochondria. The CPT1A P479L variant is found in high frequencies among indigenous populations residing on the west and north coasts of Alaska and Canada and in northeast Siberia and Greenland. Epidemiological studies have reported a statistical association between P479L homozygosity and infant death in Alaska Native and Canadian Inuit populations. Here, we review the available evidence about the P479L variant and apply to these data the epidemiological criteria for assessing causal associations. We find insufficient evidence to support a causal association with infant death and further, that if a causal association is present, the genotype is likely to be only one of a complex set of factors contributing to an increased risk of infant death. We conclude that additional research is needed to clarify the observed association and to inform effective preventative measures for infant death. In light of these findings, we discuss the policy implications for public health efforts, as policies based on the observed association between P479L homozygosity and infant death data are premature. PMID:28125087

Individual, physical and psychological risk factors for neck pain in Australian office workers: a 1-year longitudinal study.

PubMed

Hush, Julia M; Michaleff, Zoe; Maher, Christopher G; Refshauge, Kathryn

2009-10-01

Neck pain is more prevalent in office workers than in the general community. To date, findings from prospective studies that investigated causal relationships between putative risk factors and the onset of neck pain in this population have been limited by high loss to follow-up. The aim of this research was to prospectively evaluate a range of risk factors for neck pain in office workers, using validated and reliable objective measures as well as attain an estimate of 1-year incidence. We assembled a cohort of 53 office workers without neck pain and measured individual, physical, workplace and psychological factors at baseline. We followed participants for 1 year to measure the incidence of neck pain. We achieved 100% participant follow-up. Cox regression analysis was applied to examine the relationship between the putative risk factors and the cumulative incidence of neck pain. The 1-year incidence proportion of neck pain in Australian office workers was estimated in this study to be 0.49 (95% CI 0.36-0.62). Predictors of neck pain with moderate to large effect sizes were female gender (HR: 3.07; 95% CI: 1.18-7.99) and high psychological stress (HR: 1.64; 95% CI: 0.66-4.07). Protective factors included increased mobility of the cervical spine (HR: 0.44; 95% CI: 0.19-1.05) and frequent exercise (HR: 0.64; 95% CI: 0.27-1.51). These results reveal that neck pain is common in Australian office workers and that there are risk factors that are potentially modifiable.

Role of Ureaplasma Respiratory Tract Colonization in BPD Pathogenesis: Current Concepts and Update

PubMed Central

Viscardi, Rose Marie; Kallapur, Suhas G.

2015-01-01

SYNOPSIS Respiratory tract colonization with the genital mycoplasma species Ureaplasma parvum and U. urealyticum in preterm infants is a significant risk factor for BPD. Recent studies of the ureaplasmal genome, animal infection models, and human infants have provided a better understanding of specific virulence factors, pathogen-host interactions, and variability in genetic susceptibility that contribute to chronic infection, inflammation, and altered lung development. This review will provide an update on the current evidence supporting a causal role of Ureaplasma infection in BPD pathogenesis. The current status of antibiotic trials to prevent BPD in Ureaplasma-infected preterm infants is also reviewed. PMID:26593075

Effects of the Ambient Fine Particulate Matter on Public Awareness of Lung Cancer Risk in China: Evidence from the Internet-Based Big Data Platform.

PubMed

Yang, Hongxi; Li, Shu; Sun, Li; Zhang, Xinyu; Hou, Jie; Wang, Yaogang

2017-10-03

In October 2013, the International Agency for Research on Cancer classified the particulate matter from outdoor air pollution as a group 1 carcinogen and declared that particulate matter can cause lung cancer. Fine particular matter (PM 2.5 ) pollution is becoming a serious public health concern in urban areas of China. It is essential to emphasize the importance of the public's awareness and knowledge of modifiable risk factors of lung cancer for prevention. The objective of our study was to explore the public's awareness of the association of PM 2.5 with lung cancer risk in China by analyzing the relationship between the daily PM 2.5 concentration and searches for the term "lung cancer" on an Internet big data platform, Baidu. We collected daily PM 2.5 concentration data and daily Baidu Index data in 31 Chinese capital cities from January 1, 2014 to December 31, 2016. We used Spearman correlation analysis to explore correlations between the daily Baidu Index for lung cancer searches and the daily average PM 2.5 concentration. Granger causality test was used to analyze the causal relationship between the 2 time-series variables. In 23 of the 31 cities, the pairwise correlation coefficients (Spearman rho) between the daily Baidu Index for lung cancer searches and the daily average PM 2.5 concentration were positive and statistically significant (P<.05). However, the correlation between the daily Baidu Index for lung cancer searches and the daily average PM 2.5 concentration was poor (all r 2 s <.1). Results of Granger causality testing illustrated that there was no unidirectional causality from the daily PM 2.5 concentration to the daily Baidu Index for lung cancer searches, which was statistically significant at the 5% level for each city. The daily average PM 2.5 concentration had a weak positive impact on the daily search interest for lung cancer on the Baidu search engine. Well-designed awareness campaigns are needed to enhance the general public's awareness of the association of PM 2.5 with lung cancer risk, to lead the public to seek more information about PM 2.5 and its hazards, and to cope with their environment and its risks appropriately. ©Hongxi Yang, Shu Li, Li Sun, Xinyu Zhang, Jie Hou, Yaogang Wang. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 03.10.2017.

Supporting shared hypothesis testing in the biomedical domain.

PubMed

Agibetov, Asan; Jiménez-Ruiz, Ernesto; Ondrésik, Marta; Solimando, Alessandro; Banerjee, Imon; Guerrini, Giovanna; Catalano, Chiara E; Oliveira, Joaquim M; Patanè, Giuseppe; Reis, Rui L; Spagnuolo, Michela

2018-02-08

Pathogenesis of inflammatory diseases can be tracked by studying the causality relationships among the factors contributing to its development. We could, for instance, hypothesize on the connections of the pathogenesis outcomes to the observed conditions. And to prove such causal hypotheses we would need to have the full understanding of the causal relationships, and we would have to provide all the necessary evidences to support our claims. In practice, however, we might not possess all the background knowledge on the causality relationships, and we might be unable to collect all the evidence to prove our hypotheses. In this work we propose a methodology for the translation of biological knowledge on causality relationships of biological processes and their effects on conditions to a computational framework for hypothesis testing. The methodology consists of two main points: hypothesis graph construction from the formalization of the background knowledge on causality relationships, and confidence measurement in a causality hypothesis as a normalized weighted path computation in the hypothesis graph. In this framework, we can simulate collection of evidences and assess confidence in a causality hypothesis by measuring it proportionally to the amount of available knowledge and collected evidences. We evaluate our methodology on a hypothesis graph that represents both contributing factors which may cause cartilage degradation and the factors which might be caused by the cartilage degradation during osteoarthritis. Hypothesis graph construction has proven to be robust to the addition of potentially contradictory information on the simultaneously positive and negative effects. The obtained confidence measures for the specific causality hypotheses have been validated by our domain experts, and, correspond closely to their subjective assessments of confidences in investigated hypotheses. Overall, our methodology for a shared hypothesis testing framework exhibits important properties that researchers will find useful in literature review for their experimental studies, planning and prioritizing evidence collection acquisition procedures, and testing their hypotheses with different depths of knowledge on causal dependencies of biological processes and their effects on the observed conditions.

Mindfulness and zest for life buffer the negative effects of experimentally-induced perceived burdensomeness and thwarted belongingness: Implications for theories of suicide.

PubMed

Collins, Khan R L; Best, Ida; Stritzke, Werner G K; Page, Andrew C

2016-07-01

Suicide research can be enhanced by an ability to safely manipulate putative causal variables. The present studies developed an experimental task to modify risk factors identified by the interpersonal theory of suicide (perceived burdensomeness and thwarted belongingness) and examine their hypothesized suppressive effect on persistence in adversity in undergraduate university students. Variables that may moderate the impact of these risk factors on persistence (zest for life and mindful awareness) were incorporated as potential resilience factors. Study 1 (N = 92) found elevated burdensomeness and diminished belongingness significantly impaired persistence. Additionally, these predicted effects were moderated by individual differences in zest for life. In Study 2 (N = 52), individuals trained in mindfulness prior to the experimental task displayed greater persistence relative to controls. Findings provide experimental support for the role of perceived burdensomeness and thwarted belongingness in the manner predicted by the interpersonal theory, and demonstrate a way to experimentally test the effects of resilience factors that reduce the impact of these interpersonal factors. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Risk Perception and Risk-Taking Behaviour during Adolescence: The Influence of Personality and Gender.

PubMed

Reniers, Renate L E P; Murphy, Laura; Lin, Ashleigh; Bartolomé, Sandra Para; Wood, Stephen J

2016-01-01

This study investigated the influence of personality characteristics and gender on adolescents' perception of risk and their risk-taking behaviour. Male and female participants (157 females: 116 males, aged 13-20) completed self-report measures on risk perception, risk-taking and personality. Male participants perceived behaviours as less risky, reportedly took more risks, were less sensitive to negative outcomes and less socially anxious than female participants. Path analysis identified a model in which age, behavioural inhibition and impulsiveness directly influenced risk perception, while age, social anxiety, impulsiveness, sensitivity to reward, behavioural inhibition and risk perception itself were directly or indirectly associated with risk-taking behaviour. Age and behavioural inhibition had direct relationships with social anxiety, and reward sensitivity was associated with impulsiveness. The model was representative for the whole sample and male and female groups separately. The observed relationship between age and social anxiety and the influence this may have on risk-taking behaviour could be key for reducing adolescent risk-taking behaviour. Even though adolescents may understand the riskiness of their behaviour and estimate their vulnerability to risk at a similar level to adults, factors such as anxiety regarding social situations, sensitivity to reward and impulsiveness may exert their influence and make these individuals prone to taking risks. If these associations are proven causal, these factors are, and will continue to be, important targets in prevention and intervention efforts.

Risk Perception and Risk-Taking Behaviour during Adolescence: The Influence of Personality and Gender

PubMed Central

Reniers, Renate L. E. P.; Murphy, Laura; Lin, Ashleigh; Bartolomé, Sandra Para; Wood, Stephen J.

2016-01-01

This study investigated the influence of personality characteristics and gender on adolescents’ perception of risk and their risk-taking behaviour. Male and female participants (157 females: 116 males, aged 13–20) completed self-report measures on risk perception, risk-taking and personality. Male participants perceived behaviours as less risky, reportedly took more risks, were less sensitive to negative outcomes and less socially anxious than female participants. Path analysis identified a model in which age, behavioural inhibition and impulsiveness directly influenced risk perception, while age, social anxiety, impulsiveness, sensitivity to reward, behavioural inhibition and risk perception itself were directly or indirectly associated with risk-taking behaviour. Age and behavioural inhibition had direct relationships with social anxiety, and reward sensitivity was associated with impulsiveness. The model was representative for the whole sample and male and female groups separately. The observed relationship between age and social anxiety and the influence this may have on risk-taking behaviour could be key for reducing adolescent risk-taking behaviour. Even though adolescents may understand the riskiness of their behaviour and estimate their vulnerability to risk at a similar level to adults, factors such as anxiety regarding social situations, sensitivity to reward and impulsiveness may exert their influence and make these individuals prone to taking risks. If these associations are proven causal, these factors are, and will continue to be, important targets in prevention and intervention efforts. PMID:27100081

Confounding factors in determining causal soil moisture-precipitation feedback

NASA Astrophysics Data System (ADS)

Tuttle, Samuel E.; Salvucci, Guido D.

2017-07-01

Identification of causal links in the land-atmosphere system is important for construction and testing of land surface and general circulation models. However, the land and atmosphere are highly coupled and linked by a vast number of complex, interdependent processes. Statistical methods, such as Granger causality, can help to identify feedbacks from observational data, independent of the different parameterizations of physical processes and spatiotemporal resolution effects that influence feedbacks in models. However, statistical causal identification methods can easily be misapplied, leading to erroneous conclusions about feedback strength and sign. Here, we discuss three factors that must be accounted for in determination of causal soil moisture-precipitation feedback in observations and model output: seasonal and interannual variability, precipitation persistence, and endogeneity. The effect of neglecting these factors is demonstrated in simulated and observational data. The results show that long-timescale variability and precipitation persistence can have a substantial effect on detected soil moisture-precipitation feedback strength, while endogeneity has a smaller effect that is often masked by measurement error and thus is more likely to be an issue when analyzing model data or highly accurate observational data.

Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer

PubMed Central

Lawrenson, Kate; Iversen, Edwin S.; Tyrer, Jonathan; Weber, Rachel Palmieri; Concannon, Patrick; Hazelett, Dennis J.; Li, Qiyuan; Marks, Jeffrey R.; Berchuck, Andrew; Lee, Janet M.; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Chen, Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Plisiecka-Halasa, Joanna; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Gronwald, Jacek; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Jakubowska, Anna; Paul, James; Jensen, Allan; Karlan, Beth Y.; Kjaer, Susanne Kruger; Kelemen, Linda E.; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Cannioto, Rikki; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; Nevanlinna, Heli; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Noor Azmi, Mat Adenan; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Phelan, Catherine M.; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Budzilowska, Agnieszka; Sellers, Thomas A.; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Timorek, Agnieszka; Tworoger, Shelley S.; Nieuwenhuysen, Els Van; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Coetzee, Gerhard A.; Freedman, Matthew L.; Monteiro, Alvaro N.A.; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta; Pharoah, Paul D.; Gayther, Simon A.; Schildkraut, Joellen M.

2015-01-01

Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10–7). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r 2 with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11–1.24, P = 1.1×10−7). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10−8). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r 2 = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10-8). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene. PMID:26424751

Risk factors for cryptorchidism

PubMed Central

Gurney, Jason K.; McGlynn, Katherine A.; Stanley, James; Merriman, Tony; Signal, Virginia; Shaw, Caroline; Edwards, Richard; Richiardi, Lorenzo; Hutson, John; Sarfati, Diana

2018-01-01

The condition known as cryptorchidism – undescended testis – is one of the most common congenital abnormalities found among males, and is one of the few known risk factors for testicular cancer (TC). Like testicular cancer, the key exposures in the occurrence of cryptorchidism remain elusive. Testicular descent is thought to occur during two hormonally-controlled phases – between 8–15 weeks and 25–35 weeks gestation – and while it is clear that a failure of testes to descend permanently is likely due to disruptions to one or both of these phases, the cause(s) and mechanism(s) of such disruption are still unclear. In this manuscript, we review the broad range of putative risk factors that have been evaluated in relation to the development of cryptorchidism to date, discuss their plausibility, and make suggestions regarding further approaches to understand aetiology. There are few exposures for which there is consistent evidence of an association with cryptorchidism; and in those cases where evidence appears unequivocal – for example, the relationship between cryptorchidism and gestational measures such as low birth weight – the measured exposure is likely to be a surrogate for the true causal exposure. The relative importance of each risk factor may vary considerably between mother/son pairs depending on an array of genetic, maternal, placental and foetal factors – all of which could vary between regions. PMID:28654092

The Model Analyst’s Toolkit: Scientific Model Development, Analysis, and Validation

DTIC Science & Technology

2013-11-20

Granger causality F-test validation 3.1.2. Dynamic time warping for uneven temporal relationships Many causal relationships are imperfectly...mapping for dynamic feedback models Granger causality and DTW can identify causal relationships and consider complex temporal factors. However, many ...variant of the tf-idf algorithm (Manning, Raghavan, Schutze et al., 2008), typically used in search engines, to “score” features. The (-log tf) in

Proton-pump inhibitors: understanding the complications and risks.

PubMed

Malfertheiner, Peter; Kandulski, Arne; Venerito, Marino

2017-12-01

Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection. As discussed in this Review, most associations of PPIs with severe adverse events are not based on sufficient evidence because of confounding factors and a lack of plausible mechanisms. Thus, a causal relationship remains unproven in most associations, and further studies are needed. Awareness of PPI-associated risks should not lead to anxiety in patients but rather should induce the physician to consider the appropriate dosing and duration of PPI therapy, including long-term monitoring strategies in selected groups of patients because of their individual comorbidities and risk factors.

A cross-sectional study of the relationship between job demand-control, effort-reward imbalance and cardiovascular heart disease risk factors.

PubMed

Söderberg, Mia; Rosengren, Annika; Hillström, Jenny; Lissner, Lauren; Torén, Kjell

2012-12-21

This cross-sectional study explored relationships between psychosocial work environment, captured by job demand-control (JDC) and effort-reward imbalance (ERI), and seven cardiovascular heart disease (CHD) risk factors in a general population. The sampled consists of randomly-selected men and women from Gothenburg, Sweden and the city's surrounding metropolitan areas. Associations between psychosocial variables and biomarkers were analysed with multiple linear regression adjusted for age, smoking, education and occupational status. The study included 638 men and 668 women aged 24-71. Analysis between JDC and CHD risk factors illustrated that, for men, JDC was associated with impaired scores in several biomarkers, especially among those in high strain jobs. For women, there were no relationships between JDC and biomarkers. In the analysis of links between ERI and CHD risk factors, most associations tested null. The only findings were raised triglycerides and BMI among men in the fourth quartile of the ERI-ratio distribution, and lowered LDL-cholesterol for women. An complementary ERI analysis, combining high/low effort and reward into categories, illustrated lowered triglycerides and elevated HDL-cholesterol values among women reporting high efforts and high rewards, compared to women experiencing low effort and high reward. There were some associations between psychosocial stressors and CHD risk factors. The cross-sectional design did not allow conclusions about causality but some results indicated gender differences regarding sensitivity to work stressors and also how the models might capture different psychosocial dimensions.

Causality in criminal forensic and in civil disability cases: Legal and psychological comparison.

PubMed

Young, Gerald

2015-01-01

Causality (or causation) is central to every legal case, yet its underlying philosophical, legal, and psychological definitions and conceptions vary. In the criminal context, it refers to establishing the responsibility of the perpetrator of the criminal act at issue in terms of the person's mental state (mens rea), and whether the insanity defense applies. In the forensic disability and related context, it refers to whether the index event is a material or contributing cause in the multifactorial array that led to the psychological condition at issue. In both the criminal and tort contexts, the legal test is a counterfactual one. For the former, it refers to whether the outcome involved would have resulted absent the act (e.g., in cases of simultaneous criminal lethal action, which one is the but-for responsible one). For the latter, it concerns whether the claimed psychological condition would be present only because of the incident at issue. The latter event at issue is distinguished from the criminal one by its negligence compared to the voluntary intent in the criminal case. The psychological state of the perpetrator of criminal conduct can be analyzed from a biopsychosocial perspective as much as the civil one. In this regard, in the civil case, such as in forensic disability and related assessments, pre-existing, precipitating, and perpetuating factors need to be considered causally, with personal and social resilience and protective factors added, as well. In the criminal context, the same biopsychosocial model applies, but with mental competence and voluntariness added as a critical factor. The advent of neurolaw has led to use of neuroscience in court, but it risks reducing the complexity of criminal cases to unifactorial, biological models. Copyright © 2015 Elsevier Ltd. All rights reserved.

Investigating the possible causal role of coffee consumption with prostate cancer risk and progression using Mendelian randomization analysis

PubMed Central

Martin, Richard M.; Geybels, Milan S.; Stanford, Janet L.; Shui, Irene; Eeles, Rosalind; Easton, Doug; Kote‐Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay‐Tee; Blot, William; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon‐Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Donovan, Jenny; Munafò, Marcus R.

2016-01-01

Coffee consumption has been shown in some studies to be associated with lower risk of prostate cancer. However, it is unclear if this association is causal or due to confounding or reverse causality. We conducted a Mendelian randomisation analysis to investigate the causal effects of coffee consumption on prostate cancer risk and progression. We used two genetic variants robustly associated with caffeine intake (rs4410790 and rs2472297) as proxies for coffee consumption in a sample of 46,687 men of European ancestry from 25 studies in the PRACTICAL consortium. Associations between genetic variants and prostate cancer case status, stage and grade were assessed by logistic regression and with all‐cause and prostate cancer‐specific mortality using Cox proportional hazards regression. There was no clear evidence that a genetic risk score combining rs4410790 and rs2472297 was associated with prostate cancer risk (OR per additional coffee increasing allele: 1.01, 95% CI: 0.98,1.03) or having high‐grade compared to low‐grade disease (OR: 1.01, 95% CI: 0.97,1.04). There was some evidence that the genetic risk score was associated with higher odds of having nonlocalised compared to localised stage disease (OR: 1.03, 95% CI: 1.01, 1.06). Amongst men with prostate cancer, there was no clear association between the genetic risk score and all‐cause mortality (HR: 1.00, 95% CI: 0.97,1.04) or prostate cancer‐specific mortality (HR: 1.03, 95% CI: 0.98,1.08). These results, which should have less bias from confounding than observational estimates, are not consistent with a substantial effect of coffee consumption on reducing prostate cancer incidence or progression. PMID:27741566

Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies.

PubMed

Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira; Katsoulis, Michail; Freisling, Heinz; Jenab, Mazda; Gunter, Marc J; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Bueno-De-Mesquita, H Bas; Chong, Dawn Q; Jensen, Majken K; Wu, Chunsen; Overvad, Kim; Kühn, Tilman; Barrdahl, Myrto; Melander, Olle; Jirström, Karin; Peeters, Petra H; Sieri, Sabina; Panico, Salvatore; Cross, Amanda J; Riboli, Elio; Van Guelpen, Bethany; Myte, Robin; Huerta, José María; Rodriguez-Barranco, Miguel; Quirós, José Ramón; Dorronsoro, Miren; Tjønneland, Anne; Olsen, Anja; Travis, Ruth; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Severi, Gianluca; Bonet, Catalina; Palli, Domenico; Janke, Jürgen; Lee, Young-Ae; Boeing, Heiner; Giovannucci, Edward L; Ogino, Shuji; Fuchs, Charles S; Rimm, Eric; Wu, Kana; Chan, Andrew T; Pischon, Tobias

2017-05-01

Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.

Developmental dyslexia: predicting individual risk

PubMed Central

Thompson, Paul A; Hulme, Charles; Nash, Hannah M; Gooch, Debbie; Hayiou-Thomas, Emma; Snowling, Margaret J

2015-01-01

Background Causal theories of dyslexia suggest that it is a heritable disorder, which is the outcome of multiple risk factors. However, whether early screening for dyslexia is viable is not yet known. Methods The study followed children at high risk of dyslexia from preschool through the early primary years assessing them from age 3 years and 6 months (T1) at approximately annual intervals on tasks tapping cognitive, language, and executive-motor skills. The children were recruited to three groups: children at family risk of dyslexia, children with concerns regarding speech, and language development at 3;06 years and controls considered to be typically developing. At 8 years, children were classified as ‘dyslexic’ or not. Logistic regression models were used to predict the individual risk of dyslexia and to investigate how risk factors accumulate to predict poor literacy outcomes. Results Family-risk status was a stronger predictor of dyslexia at 8 years than low language in preschool. Additional predictors in the preschool years include letter knowledge, phonological awareness, rapid automatized naming, and executive skills. At the time of school entry, language skills become significant predictors, and motor skills add a small but significant increase to the prediction probability. We present classification accuracy using different probability cutoffs for logistic regression models and ROC curves to highlight the accumulation of risk factors at the individual level. Conclusions Dyslexia is the outcome of multiple risk factors and children with language difficulties at school entry are at high risk. Family history of dyslexia is a predictor of literacy outcome from the preschool years. However, screening does not reach an acceptable clinical level until close to school entry when letter knowledge, phonological awareness, and RAN, rather than family risk, together provide good sensitivity and specificity as a screening battery. PMID:25832320

The Singaporean public beliefs about the causes of mental illness: results from a multi-ethnic population-based study.

PubMed

Pang, S; Subramaniam, M; Lee, S P; Lau, Y W; Abdin, E; Chua, B Y; Picco, L; Vaingankar, J A; Chong, S A

2017-04-03

To identify the common causal beliefs of mental illness in a multi-ethnic Southeast Asian community and describe the sociodemographic associations to said beliefs. The factor structure to the causal beliefs scale is explored. The causal beliefs relating to five different mental illnesses (alcohol abuse, depression, obsessive-compulsive disorder (OCD), dementia and schizophrenia) and desire for social distance are also investigated. Data from 3006 participants from a nationwide vignette-based study on mental health literacy were analysed using factor analysis and multiple logistic regression to address the aims. Participants answered questions related to sociodemographic information, causal beliefs of mental illness and their desire for social distance towards those with mental illness. Physical causes, psychosocial causes and personality causes were endorsed by the sample. Sociodemographic differences including ethnic, gender and age differences in causal beliefs were found in the sample. Differences in causal beliefs were shown across different mental illness vignettes though psychosocial causes was the most highly attributed cause across vignettes (endorsed by 97.9% of respondents), followed by personality causes (83.5%) and last, physical causes (37%). Physical causes were more likely to be endorsed for OCD, depression and schizophrenia. Psychosocial causes were less often endorsed for OCD. Personality causes were less endorsed for dementia but more associated with depression. The factor structure of the causal beliefs scale is not entirely the same as that found in previous research. Further research on the causal beliefs endorsed by Southeast Asian communities should be conducted to investigate other potential causes such as biogenetic factors and spiritual/supernatural causes. Mental health awareness campaigns should address causes of mental illness as a topic. Lay beliefs in the different causes must be acknowledged and it would be beneficial for the public to be informed of the causes of some of the most common mental illnesses in order to encourage help-seeking and treatment compliance.

Risk factors for anal human papillomavirus infection type 16 among HIV-positive men who have sex with men in San Francisco

PubMed Central

Hernandez, Alexandra L.; Efird, Jimmy T.; Holly, Elizabeth A.; Berry, J. Michael; Jay, Naomi; Palefsky, Joel M.

2015-01-01

Background and Objective HIV-positive men who have sex with men (MSM) are at high risk of anal cancer compared with the general population. Human papillomavirus (HPV) infection, particularly HPV 16, is causally associated with anal cancer. However, risk factors for anal HPV 16 infection are poorly understood. We determined the prevalence and risk factors for anal HPV 16 infection in a population of HIV-positive MSM, most of whom were being treated with antiretroviral therapy. Design Cross-sectional data from the baseline visit of a 4-year prospective cohort study. Methods 348 HIV-positive MSM were recruited in San Francisco and received a detailed sexual behavior risk-factor questionnaire. An anal swab was used to collect specimens for HPV type-specific DNA testing using L1 HPV DNA PCR. We used log-binomial multivariable models to determine risk factors for anal HPV 16 infection. Results 92% of HIV-positive MSM had at least one anal HPV type, 80% had at least one oncogenic HPV type and 42% had HPV 16. Non-Hispanic white race and higher level of education were associated with a decreased risk of HPV 16 infection. A higher number of total male partners was associated with HPV 16 (RR: 1.6, 95%CI 1.1–2.4, p=0.01) for 201–1000 partners compared with 1–200. Injection drug use (IDU) was independently associated with anal HPV 16 infection (RR: 1.5, 95%CI 1.2–1.9, p=0.003). Conclusions The prevalence of anal HPV infection, including HPV 16, is high in HIV-positive MSM. HIV-positive MSM should be counseled about the risk associated with increased partners and IDU. PMID:23614994

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

PubMed

Hansen, Peter Riis

2018-01-01

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Establishing the role of rare coding variants in known Parkinson's disease risk loci.

PubMed

Jansen, Iris E; Gibbs, J Raphael; Nalls, Mike A; Price, T Ryan; Lubbe, Steven; van Rooij, Jeroen; Uitterlinden, André G; Kraaij, Robert; Williams, Nigel M; Brice, Alexis; Hardy, John; Wood, Nicholas W; Morris, Huw R; Gasser, Thomas; Singleton, Andrew B; Heutink, Peter; Sharma, Manu

2017-11-01

Many common genetic factors have been identified to contribute to Parkinson's disease (PD) susceptibility, improving our understanding of the related underlying biological mechanisms. The involvement of rarer variants in these loci has been poorly studied. Using International Parkinson's Disease Genomics Consortium data sets, we performed a comprehensive study to determine the impact of rare variants in 23 previously published genome-wide association studies (GWAS) loci in PD. We applied Prix fixe to select the putative causal genes underneath the GWAS peaks, which was based on underlying functional similarities. The Sequence Kernel Association Test was used to analyze the joint effect of rare, common, or both types of variants on PD susceptibility. All genes were tested simultaneously as a gene set and each gene individually. We observed a moderate association of common variants, confirming the involvement of the known PD risk loci within our genetic data sets. Focusing on rare variants, we identified additional association signals for LRRK2, STBD1, and SPATA19. Our study suggests an involvement of rare variants within several putatively causal genes underneath previously identified PD GWAS peaks. Copyright © 2017 Elsevier Inc. All rights reserved.

Protocol for a Controlled Experiment to Identify the Causal Role of Acute Alcohol Consumption in Condomless Sex among HIV-Positive MSM: Study Procedures, Ethical Considerations, and Implications for HIV Prevention.

PubMed

Shuper, Paul A; Joharchi, Narges; Rehm, Jürgen

2016-01-01

Although alcohol consumption is frequently perceived as a driver of condomless sex and subsequent HIV acquisition, the causal nature of this relationship remains unclear, and little is known about alcohol's direct versus indirect impact on the sexual risk dynamics of those who are HIV-positive. To address this gap, we present the protocol for an in-progress NIAAA-funded controlled experiment, wherein a sample of HIV-positive men-who-have-sex-with-men (MSM) undergoes an alcohol consumption manipulation (alcohol/placebo/control) and sexual arousal induction (sexually aroused/non-aroused), and then reports intentions to engage in condom-protected and condomless sexual acts with hypothetical sexual partners differing in HIV serostatus (HIV+/HIV-/HIV status unknown), condom use preference (use/don't use/not stated), and physical attractiveness (attractive/unattractive). Study outcomes will identify alcohol's impact on HIV-positive MSM's condomless sex intentions in the context of experimentally-manipulated factors as well as risk-relevant personality traits and alcohol-related expectancies. Detailed experimental procedures, ethical considerations, and potential implications for HIV prevention are discussed.

Spontaneous Bleeding Associated with Ginkgo biloba

PubMed Central

Bent, Stephen; Goldberg, Harley; Padula, Amy; Avins, Andrew L

2005-01-01

BACKGROUND Ginkgo biloba (ginkgo) is a herbal remedy used by over 2% of the adult population in the United States. Several review articles have suggested that ginkgo may increase the risk of bleeding. OBJECTIVE To report a case of bleeding associated with using ginkgo, to systematically review the literature for similar case reports, and to evaluate whether using ginkgo is causally related to bleeding. DATA SOURCES We searched MEDLINE, EMBASE, IBIDS, and the Cochrane Collaboration Database from 1966 to October 2004 with no language restrictions. REVIEW METHODS Published case reports of bleeding events in persons using ginkgo were selected. Two reviewers independently abstracted a standard set of information to assess whether ginkgo caused the bleeding event. RESULTS Fifteen published case reports described a temporal association between using ginkgo and a bleeding event. Most cases involved serious medical conditions, including 8 episodes of intracranial bleeding. However, 13 of the case reports identified other risk factors for bleeding. Only 6 reports clearly described that ginkgo was stopped and that bleeding did not recur. Bleeding times, measured in 3 reports, were elevated when patients were taking ginkgo. CONCLUSION A structured assessment of published case reports suggests a possible causal association between using ginkgo and bleeding events. Given the widespread use of this herb and the serious nature of the reported events, further studies are needed. Patients using ginkgo, particularly those with known bleeding risks, should be counseled about a possible increase in bleeding risk. PMID:16050865

Risk Factors Associated with Severity of Nongenetic Intellectual Disability (Mental Retardation) among Children Aged 2–18 Years Attending Kenyatta National Hospital

PubMed Central

Chege, Margaret Njambi; Odhiambo, Eunice Ajode

2018-01-01

Background Many of the nongenetic causal risk factors of intellectual disability (ID) can be prevented if they are identified early. There is paucity on information regarding potential risk factors associated with this condition in Kenya. This study aimed to establish risk factors associated with severity of nongenetic intellectual disability (ID) among children presenting with this condition at Kenyatta National Hospital (KNH). Methods A hospital-based cross-sectional study was conducted over the period between March and June 2017 in pediatric and child/youth mental health departments of Kenyatta National Hospital (KNH), Kenya. It included children aged 2–18 years diagnosed with ID without underlying known genetic cause. Results Of 97 patients with nongenetic ID, 24% had mild ID, 40% moderate, 23% severe-profound, and 10% unspecified ID. The mean age of children was 5.6 (±3.6) years. Male children were predominant (62%). Three independent factors including “labor complications” [AOR = 9.45, 95% CI = 1.23–113.29, P = 0.036], “admission to neonatal intensive care unit” [AOR = 8.09, 95% CI = 2.11–31.07, P = 0.002], and “cerebral palsy” [AOR = 21.18, CI = 4.18–107.40, P ≤ 0.001] were significantly associated with increased risk of severe/profound nongenetic ID. Conclusion The present study findings suggest that perinatal complications as well as postnatal insults are associated with increased risk of developing severe-profound intellectual disability, implying that this occurrence may be reduced with appropriate antenatal, perinatal, and neonatal healthcare interventions. PMID:29850243

Climate change, extinction risks, and reproduction of terrestrial vertebrates.

PubMed

Carey, Cynthia

2014-01-01

This review includes a broad, but superficial, summary of our understanding about current and future climate changes, the predictions about how these changes will likely affect the risks of extinction of organisms, and how current climate changes are already affecting reproduction in terrestrial vertebrates. Many organisms have become extinct in the last century, but habitat destruction, disease and man-made factors other than climate change have been implicated as the causal factor in almost all of these. Reproduction is certain to be negatively impacted in all vertebrate groups for a variety of reasons, such as direct thermal and hydric effects on mortality of embryos, mismatches between optimal availability of food supplies, frequently determined by temperature, and reproductive capacities, sometimes determined by rigid factors such as photoperiod, and disappearance of appropriate foraging opportunities, such as melting sea ice. The numbers of studies documenting correlations between climate changes and biological phenomena are rapidly increasing, but more direct information about the consequences of these changes for species survival and ecosystem health is needed than is currently available.

Psychosocial Factors Associated With Suicide Attempts, Ideation, and Future Risk in Lesbian, Gay, and Bisexual Youth.

PubMed

Rimes, Katharine A; Shivakumar, Sandhya; Ussher, Greg; Baker, Dan; Rahman, Qazi; West, Elizabeth

2018-06-21

Lesbian, gay, and bisexual (LGB) youth have elevated suicidality rates. To investigate LGB-related and other factors associated with suicide attempts, suicidal ideation, and future suicide risk in a large UK sample. Logistic regression was used to investigate factors associated with suicidality in 3,275 LGB young adults from the Youth Chances project. Suicide attempts (lifetime) were reported by 13.6% of participants; 45.2 % had suicidal ideation in the past year and 9.5% said future suicide attempts were likely. LGB stigma and discrimination experiences were significantly associated with all three aspects of suicidality. These included school stigma factors (e.g., teachers not speaking out against prejudice, lessons being negative about sexual minorities), negative reactions to coming out from family and friends, and LGB-related harassment or crime experiences. Bisexuality, not feeling accepted where one lives, younger sexual minority identification, and younger coming out were also associated with suicidality. Significant non-LGB factors included female gender, lower social support, anxiety/depression help-seeking, experiences of abuse/violence, and sexual abuse. This study is cross-sectional and further research is needed to test out whether any of these factors have a causal relationship with suicidality. A wide range of LGB stigma and discrimination experiences are associated with increased suicidality in LGB youth. Health, social care, and education professionals supporting young people should address LGB-specific risk factors.

Lipids, inflammation, and chronic kidney disease: a SHARP perspective.

PubMed

Waters, David D; Vogt, Liffert

2018-04-01

Accumulating evidence indicates that inflammation plays a role in the initiation and progression of chronic kidney disease. In the Study of Heart and Renal Protection (SHARP) trial, higher baseline C-reactive protein and higher baseline low-density lipoprotein cholesterol levels were both associated with a higher risk of cardiovascular events, but higher baseline C-reactive protein levels were also associated with a higher risk of nonvascular events. Simvastatin/ezetimibe reduced cardiovascular events independent of baseline C-reactive protein levels. However, this observation does not exclude inflammation as a causal factor for cardiovascular disease development in chronic kidney disease patients. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

[Substance use and victimization in violent assaults].

PubMed

Marvelli, E; Grattagliano, I; Aventaggiato, L; Gagliano-Candela, R

2013-01-01

The aim of this work was to examine the role of substance use as factor which increase risk of assault. A review of the some of the most important international literature about drug-facilitated crimes is presented here. The whole part of the papers shows a relationship between substance use and risk increase of assault, particularly in family violence and rape. The effects of psychotropic substances use depend on the user's emotional state and on drugs use expectations. This prospective shows that we need to be cautious in interpreting processes of linear causality between abusive behaviour, processes of victimisation, abuses and abnormal sexual behaviours, which are related to the patient's desires, enhanced and validated by drugs.

Unified theory of Alzheimer's disease (UTAD): implications for prevention and curative therapy.

PubMed

Nehls, Michael

2016-01-01

The aim of this review is to propose a Unified Theory of Alzheimer's disease (UTAD) that integrates all key behavioural, genetic and environmental risk factors in a causal chain of etiological and pathogenetic events. It is based on three concepts that emanate from human's evolutionary history: (1) The grandmother-hypothesis (GMH), which explains human longevity due to an evolutionary advantage in reproduction by trans-generational transfer of acquired knowledge. Consequently it is argued that mental health at old-age must be the default pathway of humans' genetic program and not development of AD. (2) Therefore, mechanism like neuronal rejuvenation (NRJ) and adult hippocampal neurogenesis (AHN) that still function efficiently even at old age provide the required lifelong ability to memorize personal experiences important for survival. Cumulative evidence from a multitude of experimental and epidemiological studies indicate that behavioural and environmental risk factors, which impair productive AHN, result in reduced episodic memory performance and in reduced psychological resilience. This leads to avoidance of novelty, dysregulation of the hypothalamic-pituitary-adrenal (HPA)-axis and cortisol hypersecretion, which drives key pathogenic mechanisms of AD like the accumulation and oligomerization of synaptotoxic amyloid beta, chronic neuroinflammation and neuronal insulin resistance. (3) By applying to AHN the law of the minimum (LOM), which defines the basic requirements of biological growth processes, the UTAD explains why and how different lifestyle deficiencies initiate the AD process by impairing AHN and causing dysregulation of the HPA-axis, and how environmental and genetic risk factors such as toxins or ApoE4, respectively, turn into disease accelerators under these unnatural conditions. Consequently, the UTAD provides a rational strategy for the prevention of mental decline and a system-biological approach for the causal treatment of AD, which might even be curative if the systemic intervention is initiated early enough in the disease process. Hence an individualized system-biological treatment of patients with early AD is proposed as a test for the validity of UTAD and outlined in this review.

Biomechanical and psychosocial exposures are independent risk factors for carpal tunnel syndrome: assessment of confounding using causal diagrams.

PubMed

Harris-Adamson, Carisa; Eisen, Ellen A; Neophytou, Andreas; Kapellusch, Jay; Garg, Arun; Hegmann, Kurt T; Thiese, Matthew S; Dale, Ann Marie; Evanoff, Bradley; Bao, Stephen; Silverstein, Barbara; Gerr, Fred; Burt, Susan; Rempel, David

2016-11-01

Between 2001 and 2010, six research groups conducted coordinated prospective studies of carpal tunnel syndrome (CTS) incidence among US workers from various industries to estimate exposure-response relationships. This analysis examined the presence and magnitude of confounding between biomechanical and workplace psychosocial factors and incidence of dominant-hand CTS. 1605 participants, without CTS at enrolment, were followed for up to 3.5 years (2471 person-years). Demographic information, medical history and workplace psychosocial stress measures were collected at baseline. Individual workplace biomechanical exposures were collected for each task and combined across the workweek using time-weighted averaging (TWA). CTS case criteria were based on symptoms and results of electrophysiological testing. HRs were estimated with Cox proportional hazard models. Confounding was assessed using causal diagrams and an empirical criterion of 10% or greater change in effect estimate magnitude. There were 109 incident CTS cases (IR=4.41/100 person-years; 6.7% cumulative incidence). The relationships between CTS and forceful repetition rate, % time forceful hand exertion and the Threshold Limit Value for Hand Activity Level (TLV-HAL) were slightly confounded by decision latitude with effect estimates being attenuated towards the null (10-14% change) after adjustment. The risk of CTS among participants reporting high job strain was attenuated towards the null by 14% after adjusting for the HAL Scale or the % time forceful hand exertions. Although attenuation of the relationships between CTS and some biomechanical and work psychosocial exposures was observed after adjusting for confounding, the magnitudes were small and confirmed biomechanical and work psychosocial exposures as independent risk factors for incident CTS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Job Strain, Health and Sickness Absence: Results from the Hordaland Health Study

PubMed Central

Wang, Min-Jung; Mykletun, Arnstein; Møyner, Ellen Ihlen; Øverland, Simon; Henderson, Max; Stansfeld, Stephen; Hotopf, Matthew; Harvey, Samuel B.

2014-01-01

Objectives While it is generally accepted that high job strain is associated with adverse occupational outcomes, the nature of this relationship and the causal pathways involved are not well elucidated. We aimed to assess the association between job strain and long-term sickness absence (LTSA), and investigate whether any associations could be explained by validated health measures. Methods Data from participants (n = 7346) of the Hordaland Health Study (HUSK), aged 40–47 at baseline, were analyzed using multivariate Cox regression to evaluate the association between job strain and LTSA over one year. Further analyses examined whether mental and physical health mediated any association between job strain and sickness absence. Results A positive association was found between job strain and risk of a LTSA episode, even controlling for confounding factors (HR = 1.64 (1.36–1.98); high job strain exposure accounted for a small proportion of LTSA episodes (population attributable risk 0.068). Further adjustments for physical health and mental health individually attenuated, but could not fully explain the association. In the fully adjusted model, the association between high job strain and LTSA remained significant (HR = 1.30 (1.07–1.59)). Conclusion High job strain increases the risk of LTSA. While our results suggest that one in 15 cases of LTSA could be avoided if high job strain were eliminated, we also provide evidence against simplistic causal models. The impact of job strain on future LTSA could not be fully explained by impaired health at baseline, which suggests that factors besides ill health are important in explaining the link between job strain and sickness absence. PMID:24755878

How shift scheduling practices contribute to fatigue amongst freight rail operating employees: Findings from Canadian accident investigations.

PubMed

Rudin-Brown, Christina M; Harris, Sarah; Rosberg, Ari

2018-02-01

Canada's freight rail system moves 70% of the country's surface goods and almost half of all exports (RAC, 2016). These include dangerous goods. Anonymous survey of freight rail operating employees conducted by the Teamsters Canada Rail Conference (TCRC, 2014) revealed that many do not report getting enough sleep because of their work schedules, and that fatigue may be affecting their performance at work. Besides general impairments in attention and cognitive functioning, fatigue in railway operating employees slows reaction time to safety alarms and impairs conformance to train operating requirements. Shift scheduling practices can contribute to sleep-related fatigue by restricting sleep opportunities, requiring extended periods of wakefulness and by disrupting daily (circadian) rhythms. The primary goal of accident investigation is to identify causal and contributing factors so that similar occurrences can be prevented. A database search of Transportation Safety Board (TSB) rail investigation reports published in the 21-year period from 1995 to 2015 identified 18 that cited sleep-related fatigue of freight rail operating employees as a causal, contributing, or risk finding. This number represents about 20% of TSB rail investigations from the same period in which a human factors aspect of freight train activities was a primary cause. Exploration of accident themes suggests that management of fatigue and shift scheduling in the freight rail industry is a complex issue that is often not conducive to employee circadian rhythms and sleep requirements. It also suggests that current shift scheduling and fatigue management practices may be insufficient to mitigate the associated safety risk. Railway fatigue management systems that are based on the principles of modern sleep science are needed to improve scheduling practices and mitigate the ongoing safety risk. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver.

PubMed

Dongiovanni, P; Stender, S; Pietrelli, A; Mancina, R M; Cespiati, A; Petta, S; Pelusi, S; Pingitore, P; Badiali, S; Maggioni, M; Mannisto, V; Grimaudo, S; Pipitone, R M; Pihlajamaki, J; Craxi, A; Taube, M; Carlsson, L M S; Fargion, S; Romeo, S; Kozlitina, J; Valenti, L

2018-04-01

Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders. The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance. We performed a Mendelian randomization analysis using risk alleles in PNPLA3, TM6SF2, GCKR and MBOAT7, and a polygenic risk score for hepatic fat, as instruments. We evaluated complementary cohorts of at-risk individuals and individuals from the general population: 1515 from the liver biopsy cohort (LBC), 3329 from the Swedish Obese Subjects Study (SOS) and 4570 from the population-based Dallas Heart Study (DHS). Hepatic fat was epidemiologically associated with liver damage, insulin resistance, dyslipidemia and hypertension. The impact of genetic variants on liver damage was proportional to their effect on hepatic fat accumulation. Genetically determined hepatic fat was associated with aminotransferases, and with inflammation, ballooning and fibrosis in the LBC. Furthermore, in the LBC, the causal association between hepatic fat and fibrosis was independent of disease activity, suggesting that a causal effect of long-term liver fat accumulation on liver disease is independent of inflammation. Genetically determined hepatic steatosis was associated with insulin resistance in the LBC and SOS. However, this association was dependent on liver damage severity. Genetically determined hepatic steatosis was associated with liver fibrosis/cirrhosis and with a small increase in risk of type 2 diabetes in publicly available databases. These data suggest that long-term hepatic fat accumulation plays a causal role in the development of chronic liver disease. © 2017 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Proportion of cancer in a Middle eastern country attributable to established risk factors.

PubMed

Charafeddine, Maya A; Olson, Sara H; Mukherji, Deborah; Temraz, Sally N; Abou-Alfa, Ghassan K; Shamseddine, Ali I

2017-05-18

Providing an estimate of the percentage of cancer in Lebanon by 2018 that is due to the exposure to risk factors in 2008. Factors include: smoking, body mass index (BMI), physical inactivity, dietary factors, alcohol consumption, infections, and air pollution in adults. Population Attributable Fraction (PAF) was calculated using the proportion of the population exposed and relative risks for each risk factor from meta-analyses. The PAF estimates the proportion of cases in which exposure may have played a causal role. Smoking caused most cancer cases, and it will further add a total of 1800 new cases by 2018. Among many other cancers, lung cancer had the largest proportion attributable of around 75%. BMI is expected to increase colorectal, liver and gastric cardia carcinoma specifically in males. High physical activity has a an average of 15% protection rate on cancer on colorectal cancer. Minimal adherence to Mediterranean diet will affect gastric cancer incidence by 7%. Cases of oropharyngeal and esophageal cancer will be the result of alcohol consumption mainly in males. H.Pylori infection is expected to result in half of the gastric cases by 2018. The high exposure to air pollution is expected to contribute by 13% to lung cancer cases in 2018. The highest benefits can be achieved by controlling tobacco smoking. Interrelated and small changes in weight, physical activity and healthy diet with limited alcohol consumption can protect against several GI cancers in the long run. These results can be used to determine public health interventions that target important risk factors in the general population.

Direct and indirect effects of biological factors on extinction risk in fossil bivalves

PubMed Central

Harnik, Paul G.

2011-01-01

Biological factors, such as abundance and body size, may contribute directly to extinction risk and indirectly through their influence on other biological characteristics, such as geographic range size. Paleontological data can be used to explicitly test many of these hypothesized relationships, and general patterns revealed through analysis of the fossil record can help refine predictive models of extinction risk developed for extant species. Here, I use structural equation modeling to tease apart the contributions of three canonical predictors of extinction—abundance, body size, and geographic range size—to the duration of bivalve species in the early Cenozoic marine fossil record of the eastern United States. I find that geographic range size has a strong direct effect on extinction risk and that an apparent direct effect of abundance can be explained entirely by its covariation with geographic range. The influence of geographic range on extinction risk is manifest across three ecologically disparate bivalve clades. Body size also has strong direct effects on extinction risk but operates in opposing directions in different clades, and thus, it seems to be decoupled from extinction risk in bivalves as a whole. Although abundance does not directly predict extinction risk, I reveal weak indirect effects of both abundance and body size through their positive influence on geographic range size. Multivariate models that account for the pervasive covariation between biological factors and extinction are necessary for assessing causality in evolutionary processes and making informed predictions in applied conservation efforts. PMID:21808004

Direct and indirect effects of biological factors on extinction risk in fossil bivalves.

PubMed

Harnik, Paul G

2011-08-16

Biological factors, such as abundance and body size, may contribute directly to extinction risk and indirectly through their influence on other biological characteristics, such as geographic range size. Paleontological data can be used to explicitly test many of these hypothesized relationships, and general patterns revealed through analysis of the fossil record can help refine predictive models of extinction risk developed for extant species. Here, I use structural equation modeling to tease apart the contributions of three canonical predictors of extinction--abundance, body size, and geographic range size--to the duration of bivalve species in the early Cenozoic marine fossil record of the eastern United States. I find that geographic range size has a strong direct effect on extinction risk and that an apparent direct effect of abundance can be explained entirely by its covariation with geographic range. The influence of geographic range on extinction risk is manifest across three ecologically disparate bivalve clades. Body size also has strong direct effects on extinction risk but operates in opposing directions in different clades, and thus, it seems to be decoupled from extinction risk in bivalves as a whole. Although abundance does not directly predict extinction risk, I reveal weak indirect effects of both abundance and body size through their positive influence on geographic range size. Multivariate models that account for the pervasive covariation between biological factors and extinction are necessary for assessing causality in evolutionary processes and making informed predictions in applied conservation efforts.

Beliefs about cancer causation and prevention as a function of personal and family history of cancer: a national, population-based study.

PubMed

Lykins, Emily L B; Graue, Lili O; Brechting, Emily H; Roach, Abbey R; Gochett, Celestine G; Andrykowski, Michael A

2008-10-01

Research suggests individuals possess multifaceted cognitive representations of various diseases. These illness representations consist of various beliefs, including causal attributions for the disease, and are believed to motivate, guide, and shape health-related behavior. As little research has examined factors associated with beliefs about cancer causation, this study examined the relationship between personal and family history of cancer and beliefs about the causes and prevention of malignant disease. Data were obtained from 6369 adult respondents to the 2003 Health Information National Trends Survey, a national population-based survey. Information about personal and family history of cancer and beliefs regarding cancer causation and prevention was obtained. Results showed both a personal and family history of cancer were associated with differences in beliefs about the causes of cancer. In general, a personal history of cancer was not significantly linked to causal attributions for cancer relative to those without a personal history. In contrast, a family history of cancer tended to increase the likelihood a respondent viewed a particular cause as increasing cancer risk. Thus, personal and vicarious experience with cancer had dramatically diverging influences on attributions of cancer causation, which may be due to differing self-protection motives. Results support the belief that illness representations, in this case the causal belief component, are influenced by both personal and vicarious experience with a disease and also suggest illness representations may influence receptivity to messages and interventions designed to increase appropriate cancer risk reduction behavior. Copyright (c) 2007 John Wiley & Sons, Ltd.

Psychological Processes Mediate the Impact of Familial Risk, Social Circumstances and Life Events on Mental Health

PubMed Central

Kinderman, Peter; Schwannauer, Matthias; Pontin, Eleanor; Tai, Sara

2013-01-01

Background Despite widespread acceptance of the ‘biopsychosocial model’, the aetiology of mental health problems has provoked debate amongst researchers and practitioners for decades. The role of psychological factors in the development of mental health problems remains particularly contentious, and to date there has not been a large enough dataset to conduct the necessary multivariate analysis of whether psychological factors influence, or are influenced by, mental health. This study reports on the first empirical, multivariate, test of the relationships between the key elements of the biospychosocial model of mental ill-health. Methods and Findings Participants were 32,827 (age 18–85 years) self-selected respondents from the general population who completed an open-access online battery of questionnaires hosted by the BBC. An initial confirmatory factor analysis was performed to assess the adequacy of the proposed factor structure and the relationships between latent and measured variables. The predictive path model was then tested whereby the latent variables of psychological processes were positioned as mediating between the causal latent variables (biological, social and circumstantial) and the outcome latent variables of mental health problems and well-being. This revealed an excellent fit to the data, S-B χ2 (3199, N = 23,397) = 126654·8, p<·001; RCFI = ·97; RMSEA = ·04 (·038–·039). As hypothesised, a family history of mental health difficulties, social deprivation, and traumatic or abusive life-experiences all strongly predicted higher levels of anxiety and depression. However, these relationships were strongly mediated by psychological processes; specifically lack of adaptive coping, rumination and self-blame. Conclusion These results support a significant revision of the biopsychosocial model, as psychological processes determine the causal impact of biological, social, and circumstantial risk factors on mental health. This has clear implications for policy, education and clinical practice as psychological processes such as rumination and self-blame are amenable to evidence-based psychological therapies. PMID:24146890

Psychological processes mediate the impact of familial risk, social circumstances and life events on mental health.

PubMed

Kinderman, Peter; Schwannauer, Matthias; Pontin, Eleanor; Tai, Sara

2013-01-01

Despite widespread acceptance of the 'biopsychosocial model', the aetiology of mental health problems has provoked debate amongst researchers and practitioners for decades. The role of psychological factors in the development of mental health problems remains particularly contentious, and to date there has not been a large enough dataset to conduct the necessary multivariate analysis of whether psychological factors influence, or are influenced by, mental health. This study reports on the first empirical, multivariate, test of the relationships between the key elements of the biospychosocial model of mental ill-health. Participants were 32,827 (age 18-85 years) self-selected respondents from the general population who completed an open-access online battery of questionnaires hosted by the BBC. An initial confirmatory factor analysis was performed to assess the adequacy of the proposed factor structure and the relationships between latent and measured variables. The predictive path model was then tested whereby the latent variables of psychological processes were positioned as mediating between the causal latent variables (biological, social and circumstantial) and the outcome latent variables of mental health problems and well-being. This revealed an excellent fit to the data, S-B χ(2) (3199, N = 23,397) = 126654.8, p<.001; RCFI = .97; RMSEA = .04 (.038-.039). As hypothesised, a family history of mental health difficulties, social deprivation, and traumatic or abusive life-experiences all strongly predicted higher levels of anxiety and depression. However, these relationships were strongly mediated by psychological processes; specifically lack of adaptive coping, rumination and self-blame. These results support a significant revision of the biopsychosocial model, as psychological processes determine the causal impact of biological, social, and circumstantial risk factors on mental health. This has clear implications for policy, education and clinical practice as psychological processes such as rumination and self-blame are amenable to evidence-based psychological therapies.

Adolescent Risk Taking, Cocaine Self-Administration, and Striatal Dopamine Signaling

PubMed Central

Mitchell, Marci R; Weiss, Virginia G; Beas, B Sofia; Morgan, Drake; Bizon, Jennifer L; Setlow, Barry

2014-01-01

Poor decision making and elevated risk taking, particularly during adolescence, have been strongly linked to drug use; however the causal relationships among these factors are not well understood. To address these relationships, a rat model (the Risky Decision-making Task; RDT) was used to determine whether individual differences in risk taking during adolescence predict later propensity for cocaine self-administration and/or whether cocaine self-administration causes alterations in risk taking. In addition, the RDT was used to determine how risk taking is modulated by dopamine signaling, particularly in the striatum. Results from these experiments indicated that greater risk taking during adolescence predicted greater intake of cocaine during acquisition of self-administration in adulthood, and that adult cocaine self-administration in turn caused elevated risk taking that was present following 6 weeks of abstinence. Greater adolescent risk taking was associated with lower striatal D2 receptor mRNA expression, and pharmacological activation of D2/3 receptors in the ventral, but not dorsal, striatum induced a decrease in risk taking. These findings indicate that the relationship between elevated risk taking and cocaine self-administration is bi-directional, and that low striatal D2 receptor expression may represent a predisposing factor for both maladaptive decision making and cocaine use. Furthermore, these findings suggest that striatal D2 receptors represent a therapeutic target for attenuating maladaptive decision making when choices include risk of adverse consequences. PMID:24145852

Precautionary principles: a jurisdiction-free framework for decision-making under risk.

PubMed

Ricci, Paolo F; Cox, Louis A; MacDonald, Thomas R

2004-12-01

Fundamental principles of precaution are legal maxims that ask for preventive actions, perhaps as contingent interim measures while relevant information about causality and harm remains unavailable, to minimize the societal impact of potentially severe or irreversible outcomes. Such principles do not explain how to make choices or how to identify what is protective when incomplete and inconsistent scientific evidence of causation characterizes the potential hazards. Rather, they entrust lower jurisdictions, such as agencies or authorities, to make current decisions while recognizing that future information can contradict the scientific basis that supported the initial decision. After reviewing and synthesizing national and international legal aspects of precautionary principles, this paper addresses the key question: How can society manage potentially severe, irreversible or serious environmental outcomes when variability, uncertainty, and limited causal knowledge characterize their decision-making? A decision-analytic solution is outlined that focuses on risky decisions and accounts for prior states of information and scientific beliefs that can be updated as subsequent information becomes available. As a practical and established approach to causal reasoning and decision-making under risk, inherent to precautionary decision-making, these (Bayesian) methods help decision-makers and stakeholders because they formally account for probabilistic outcomes, new information, and are consistent and replicable. Rational choice of an action from among various alternatives--defined as a choice that makes preferred consequences more likely--requires accounting for costs, benefits and the change in risks associated with each candidate action. Decisions under any form of the precautionary principle reviewed must account for the contingent nature of scientific information, creating a link to the decision-analytic principle of expected value of information (VOI), to show the relevance of new information, relative to the initial (and smaller) set of data on which the decision was based. We exemplify this seemingly simple situation using risk management of BSE. As an integral aspect of causal analysis under risk, the methods developed in this paper permit the addition of non-linear, hormetic dose-response models to the current set of regulatory defaults such as the linear, non-threshold models. This increase in the number of defaults is an important improvement because most of the variants of the precautionary principle require cost-benefit balancing. Specifically, increasing the set of causal defaults accounts for beneficial effects at very low doses. We also show and conclude that quantitative risk assessment dominates qualitative risk assessment, supporting the extension of the set of default causal models.

Potential health gains and health losses in eleven EU countries attainable through feasible prevalences of the life-style related risk factors alcohol, BMI, and smoking: a quantitative health impact assessment.

PubMed

Lhachimi, Stefan K; Nusselder, Wilma J; Smit, Henriette A; Baili, Paolo; Bennett, Kathleen; Fernández, Esteve; Kulik, Margarete C; Lobstein, Tim; Pomerleau, Joceline; Boshuizen, Hendriek C; Mackenbach, Johan P

2016-08-05

Influencing the life-style risk-factors alcohol, body mass index (BMI), and smoking is an European Union (EU) wide objective of public health policy. The population-level health effects of these risk-factors depend on population specific characteristics and are difficult to quantify without dynamic population health models. For eleven countries-approx. 80 % of the EU-27 population-we used evidence from the publicly available DYNAMO-HIA data-set. For each country the age- and sex-specific risk-factor prevalence and the incidence, prevalence, and excess mortality of nine chronic diseases are utilized; including the corresponding relative risks linking risk-factor exposure causally to disease incidence and all-cause mortality. Applying the DYNAMO-HIA tool, we dynamically project the country-wise potential health gains and losses using feasible, i.e. observed elsewhere, risk-factor prevalence rates as benchmarks. The effects of the "worst practice", "best practice", and the currently observed risk-factor prevalence on population health are quantified and expected changes in life expectancy, morbidity-free life years, disease cases, and cumulative mortality are reported. Applying the best practice smoking prevalence yields the largest gains in life expectancy with 0.4 years for males and 0.3 year for females (approx. 332,950 and 274,200 deaths postponed, respectively) while the worst practice smoking prevalence also leads to the largest losses with 0.7 years for males and 0.9 year for females (approx. 609,400 and 710,550 lives lost, respectively). Comparing morbidity-free life years, the best practice smoking prevalence shows the highest gains for males with 0.4 years (342,800 less disease cases), whereas for females the best practice BMI prevalence yields the largest gains with 0.7 years (1,075,200 less disease cases). Smoking is still the risk-factor with the largest potential health gains. BMI, however, has comparatively large effects on morbidity. Future research should aim to improve knowledge of how policies can influence and shape individual and aggregated life-style-related risk-factor behavior.

Automated interviews on clinical case reports to elicit directed acyclic graphs.

PubMed

Luciani, Davide; Stefanini, Federico M

2012-05-01

Setting up clinical reports within hospital information systems makes it possible to record a variety of clinical presentations. Directed acyclic graphs (Dags) offer a useful way of representing causal relations in clinical problem domains and are at the core of many probabilistic models described in the medical literature, like Bayesian networks. However, medical practitioners are not usually trained to elicit Dag features. Part of the difficulty lies in the application of the concept of direct causality before selecting all the causal variables of interest for a specific patient. We designed an automated interview to tutor medical doctors in the development of Dags to represent their understanding of clinical reports. Medical notions were analyzed to find patterns in medical reasoning that can be followed by algorithms supporting the elicitation of causal Dags. Clinical relevance was defined to help formulate only relevant questions by driving an expert's attention towards variables causally related to nodes already inserted in the graph. Key procedural features of the proposed interview are described by four algorithms. The automated interview comprises questions on medical notions, phrased in medical terms. The first elicitation session produces questions concerning the patient's chief complaints and the outcomes related to diseases serving as diagnostic hypotheses, their observable manifestations and risk factors. The second session focuses on questions that refine the initial causal paths by considering syndromes, dysfunctions, pathogenic anomalies, biases and effect modifiers. A case study concerning a gastro-enterological problem and one dealing with an infected patient illustrate the output produced by the algorithms, depending on the answers provided by the doctor. The proposed elicitation framework is characterized by strong consistency with medical background and by a progressive introduction of relevant medical topics. Revision and testing of the subjectively elicited Dag is performed by matching the collected answers with the evidence included in accepted sources of biomedical knowledge. Copyright © 2011 Elsevier B.V. All rights reserved.

The role of impaired esophageal and gastric motility in end-stage lung diseases and after lung transplantation.

PubMed

Fisichella, Piero Marco; Jalilvand, Anahita

2014-01-01

Today, many questions persist regarding the causal relationship of gastroesophageal reflux disease (GERD) to promote aspiration and its potential to induce both pulmonary and allograft failure. Current hypotheses, which have identified GERD as a nonimmune risk factor in inducing pulmonary and allograft failure, center on the role of GERD-induced aspiration of gastroduodenal contents. Risk factors of GERD, such as impaired esophageal and gastric motility, may indirectly play a role in the aspiration process. In fact, although impaired esophageal and gastric motility is not independently a cause of lung deterioration or allograft failure, they may cause and or exacerbate GERD. This report seeks to review present research on impaired esophageal and gastric motility in end-stage lung disease to characterize prevalence, etiology, pathophysiology, and current treatment options within this special patient population. Published by Elsevier Inc.

Fifty Years of Research in ARDS. Genomic Contributions and Opportunities.

PubMed

Reilly, John P; Christie, Jason D; Meyer, Nuala J

2017-11-01

Clinical factors alone poorly explain acute respiratory distress syndrome (ARDS) risk and ARDS outcome. In the search for individual factors that may influence ARDS risk, the past 20 years have witnessed the identification of numerous genes and genetic variants that are associated with ARDS. The field of ARDS genomics has cycled from candidate gene association studies to bias-free approaches that identify new candidates, and increasing effort is made to understand the functional consequences that may underlie significant associations. More recently, methodologies of causal inference are being applied to maximize the information gained from genetic associations. Although challenges of sample size, both recognized and unrecognized phenotypic heterogeneity, and the paucity of early ARDS lung tissue limit some applications of the rapidly evolving field of genomic investigation, ongoing genetic research offers unique contributions to elucidating ARDS pathogenesis and the paradigm of precision ARDS medicine.

Statins and tendinopathy: a systematic review.

PubMed

Teichtahl, Andrew J; Brady, Sharmayne R E; Urquhart, Donna M; Wluka, Anita E; Wang, Yuanyuan; Shaw, Jonathan E; Cicuttini, Flavia M

2016-02-15

To systematically review the evidence on whether statin therapy, commonly used in clinical practice to treat hypercholesterolaemia for primary and secondary prevention of cardiovascular disease, contributes to tendinopathy; and to examine causality according to the Bradford Hill criteria. A systematic review of studies examining the relationship between statin therapy and tendinopathy. Included studies were rated based on their methodological quality. A best evidence synthesis was used to summarise the results, and Bradford Hill criteria were used to assess causation. Ovid MEDLINE, CINAHL Plus, PubMed and Embase databases. We included adult human studies published in the English language between January 1966 and October 2015. Study designs eligible for inclusion were randomised controlled trials and cross-sectional, cohort or case-control studies. Four studies (three cohort studies and one case-control study) were included, with a mean methodological quality score of 67%. Three studies were deemed high quality. Tendon rupture was the primary outcome in three studies, and rotator cuff disease in the other. All studies found no positive association between statin therapy and tendon rupture for the total study population. There was evidence that simvastatin reduces the risk of tendinopathy. To date, there is a paucity of evidence to implicate statin therapy as a well established risk factor or causal mechanism for tendon rupture in the general population. There is strong evidence that simvastatin reduces the risk of tendinopathy.

Longitudinal association between cognitive performance and obsessive-compulsive symptoms in patients with psychosis and unaffected siblings.

PubMed

Schirmbeck, F; Swets, M; Meijer, C J; Zink, M; de Haan, L

2016-05-01

Obsessive-compulsive symptoms (OCS) frequently occur in psychotic disorders. Cross-sectional associations between OCS and cognitive impairment have led to different causal explanations. Whereas one assumes that higher cognitive impairment reflects a risk factor for psychotic patients to develop OCS, another suggests that deficits reflect a consequence of OCS. This study investigated the longitudinal interrelation between OCS and cognitive functioning. Baseline and follow-up data from 622 patients and 670 un-affected siblings from the 'Genetic Risk and Outcome in Psychosis' study were analyzed. Participants were allocated to groups according to the presence or absence of OCS at assessments and compared on several cognitive domains. Cross-sectional comparisons revealed no group differences in cognitive performance. Longitudinal analyses comparing the groups with changes in OCS revealed one significant group effect with more problems in set-shifting abilities in patient who reported OCS development at follow-up. Significant time and interaction effects were mainly due to improvement in immediate verbal recall and digit-symbol coding in patients and siblings who reported remission of OCS. Although insight into causality needs further exploration, our results do not confirm the hypothesis of pre-existing cognitive risk constellations. Findings suggest that remission of comorbid OCS results in improved immediate verbal recall and processing speed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Testicular microlithiasis: is there a need for surveillance in the absence of other risk factors?

PubMed

Richenberg, Jonathan; Brejt, Nick

2012-11-01

Ultrasound surveillance of patients with testicular microlithiasis (TM) has been advocated following the reported association with testicular cancer. The aim of this study was to assess the evidence base supporting such surveillance. Formal literature review identified cohort studies comprising at least 15 patients followed up for at least 24 months. Combining an institutional audit with the identified studies in a pooled analysis the incidence of new cancers during the surveillance period was evaluated. Literature review identified eight studies. Our institutional audit comprised 2,656 men referred for scrotal ultrasound. Fifty-one men (1.92 %) with TM were identified, none of whom developed testicular cancer (mean follow-up: 33.3 months). In a combined population of 389 men testicular cancer developed in 4. Excluding 3 who had additional risk factors, only 1 of 386 developed testicular cancer during follow-up (95 % CI 0.05-1.45 %). Ultrasound surveillance is unlikely to benefit patients with TM in the absence of other risk factors. In the presence of additional risk factors (previous testicular cancer, a history of maldescent or testicular atrophy) patients are likely to be under surveillance; nonetheless monthly self-examination should be encouraged, and open access to ultrasound and formal annual surveillance should be offered. • The literature reports a high association between testicular microlithiasis and testicular cancer. • Our study and meta-analysis suggest no causal link between microlithiasis and cancer. • In the absence of additional risk factors surveillance is not advocated. • In the presence of additional risk factors surveillance is recommended. • Such surveillance is primarily aimed at engaging patients in regular follow-up.

Work-relatedness of low back pain in nursing personnel: a systematic review.

PubMed

Yassi, Annalee; Lockhart, Karen

2013-01-01

Although non-specific low back pain (LBP) is known to be multifactorial, studies from across the globe have documented their higher prevalence in nurses. This systematic review was conducted to ascertain whether this much-documented association constitutes a causal relationship, and whether there is a discernible threshold of exposures associated with this elevated risk. PRISMA guidelines were followed and standard critical appraisal tools were applied. The outcome of interest was non-specific LBP or back injury; exposure was "performing nursing duties." Applicable studies, published in English during 1980-2012, were identified through database searches, screened against preset inclusion/exclusion criteria. Ergonomic assessments of nursing tasks were included along with epidemiological studies. Bradford Hill considerations for causation were utilized as a framework for discussing findings. Of 987 studies identified, 89 qualified for inclusion, comprising 21 longitudinal, 36 cross-sectional analytic, 23 descriptive biomechanical/ergonomic, and 9 review studies. Overall studies showed that nursing activities conferred increased risk for, and were associated with back disorders regardless of nursing technique, personal characteristics, and non-work-related factors. Patient handling appears to confer the highest risk, but other nursing duties are also associated with elevated risk, and confound dose-response assessments related to patient handling alone. Associations were strong, consistent, temporally possible, plausible, coherent, and analogous to other exposure-outcomes, with risk estimates ranging from 1·2 to 5·5 depending on definitions. A threshold of nursing activities below which the risk of back disorders is not elevated has not been established. Notwithstanding the bio-psycho-social nature of LBP, and complexities of studying this area, sufficient evidence exists of a causal relationship between nursing tasks and back disorders to warrant new policies.

Assessing causal mechanistic interactions: a peril ratio index of synergy based on multiplicativity.

PubMed

Lee, Wen-Chung

2013-01-01

The assessments of interactions in epidemiology have traditionally been based on risk-ratio, odds-ratio or rate-ratio multiplicativity. However, many epidemiologists fail to recognize that this is mainly for statistical conveniences and often will misinterpret a statistically significant interaction as a genuine mechanistic interaction. The author adopts an alternative metric system for risk, the 'peril'. A peril is an exponentiated cumulative rate, or simply, the inverse of a survival (risk complement) or one plus an odds. The author proposes a new index based on multiplicativity of peril ratios, the 'peril ratio index of synergy based on multiplicativity' (PRISM). Under the assumption of no redundancy, PRISM can be used to assess synergisms in sufficient cause sense, i.e., causal co-actions or causal mechanistic interactions. It has a less stringent threshold to detect a synergy as compared to a previous index of 'relative excess risk due to interaction'. Using the new PRISM criterion, many situations in which there is not evidence of interaction judged by the traditional indices are in fact corresponding to bona fide positive or negative synergisms.

Assessing Causal Mechanistic Interactions: A Peril Ratio Index of Synergy Based on Multiplicativity

PubMed Central

Lee, Wen-Chung

2013-01-01

The assessments of interactions in epidemiology have traditionally been based on risk-ratio, odds-ratio or rate-ratio multiplicativity. However, many epidemiologists fail to recognize that this is mainly for statistical conveniences and often will misinterpret a statistically significant interaction as a genuine mechanistic interaction. The author adopts an alternative metric system for risk, the ‘peril’. A peril is an exponentiated cumulative rate, or simply, the inverse of a survival (risk complement) or one plus an odds. The author proposes a new index based on multiplicativity of peril ratios, the ‘peril ratio index of synergy based on multiplicativity’ (PRISM). Under the assumption of no redundancy, PRISM can be used to assess synergisms in sufficient cause sense, i.e., causal co-actions or causal mechanistic interactions. It has a less stringent threshold to detect a synergy as compared to a previous index of ‘relative excess risk due to interaction’. Using the new PRISM criterion, many situations in which there is not evidence of interaction judged by the traditional indices are in fact corresponding to bona fide positive or negative synergisms. PMID:23826299

The Role of Epilepsy and Epileptiform EEGs in Autism Spectrum Disorders

PubMed Central

Spence, Sarah J; Schneider, Mark T

2009-01-01

Autism is a neurodevelopmental disorder of unknown etiology characterized by social and communication deficits and the presence of restricted interests/repetitive behaviors. Higher rates of epilepsy have long been reported, but prevalence estimates vary from as little as 5% to as much as 46%. This variation is probably the result of sample characteristics that increase epilepsy risk such as sample ascertainment, lower IQ, the inclusion of patients with non-idiopathic autism, age, and gender. However, critical review of the literature reveals that the rate in idiopathic cases with normal IQ is still significantly above the population risk suggesting that autism itself is associated with an increased risk of epilepsy. Recently there has been interest in the occurrence of epileptiform electroencephalograms (EEGs) even in the absence of epilepsy. Rates as high as 60% have been reported and some investigators propose that these abnormalities may play a causal role in the autism phenotype. While this phenomenon is still not well understood and risk factors have yet to be determined, the treatment implications are increasingly important. We review the recent literature to elucidate possible risk factors for both epilepsy and epileptiform EEGs. We then review existing data and discuss controversies surrounding treatment of EEG abnormalities. PMID:19454962

Causal reports: Context-dependent contributions of intuitive physics and visual impressions of launching.

PubMed

Vicovaro, Michele

2018-05-01

Everyday causal reports appear to be based on a blend of perceptual and cognitive processes. Causality can sometimes be perceived automatically through low-level visual processing of stimuli, but it can also be inferred on the basis of an intuitive understanding of the physical mechanism that underlies an observable event. We investigated how visual impressions of launching and the intuitive physics of collisions contribute to the formation of explicit causal responses. In Experiment 1, participants observed collisions between realistic objects differing in apparent material and hence implied mass, whereas in Experiment 2, participants observed collisions between abstract, non-material objects. The results of Experiment 1 showed that ratings of causality were mainly driven by the intuitive physics of collisions, whereas the results of Experiment 2 provide some support to the hypothesis that ratings of causality were mainly driven by visual impressions of launching. These results suggest that stimulus factors and experimental design factors - such as the realism of the stimuli and the variation in the implied mass of the colliding objects - may determine the relative contributions of perceptual and post-perceptual cognitive processes to explicit causal responses. A revised version of the impetus transmission heuristic provides a satisfactory explanation for these results, whereas the hypothesis that causal responses and intuitive physics are based on the internalization of physical laws does not. Copyright © 2018 Elsevier B.V. All rights reserved.

An assessment of change in risk perception and optimistic bias for hurricanes among Gulf Coast residents.

PubMed

Trumbo, Craig; Meyer, Michelle A; Marlatt, Holly; Peek, Lori; Morrissey, Bridget

2014-06-01

This study focuses on levels of concern for hurricanes among individuals living along the Gulf Coast during the quiescent two-year period following the exceptionally destructive 2005 hurricane season. A small study of risk perception and optimistic bias was conducted immediately following Hurricanes Katrina and Rita. Two years later, a follow-up was done in which respondents were recontacted. This provided an opportunity to examine changes, and potential causal ordering, in risk perception and optimistic bias. The analysis uses 201 panel respondents who were matched across the two mail surveys. Measures included hurricane risk perception, optimistic bias for hurricane evacuation, past hurricane experience, and a small set of demographic variables (age, sex, income, and education). Paired t-tests were used to compare scores across time. Hurricane risk perception declined and optimistic bias increased. Cross-lagged correlations were used to test the potential causal ordering between risk perception and optimistic bias, with a weak effect suggesting the former affects the latter. Additional cross-lagged analysis using structural equation modeling was used to look more closely at the components of optimistic bias (risk to self vs. risk to others). A significant and stronger potentially causal effect from risk perception to optimistic bias was found. Analysis of the experience and demographic variables' effects on risk perception and optimistic bias, and their change, provided mixed results. The lessening of risk perception and increase in optimistic bias over the period of quiescence suggest that risk communicators and emergency managers should direct attention toward reversing these trends to increase disaster preparedness. © 2013 Society for Risk Analysis.

Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation.

PubMed

Witsenburg, C P J; Rosendaal, F R; Middeldorp, J M; Van der Meer, F J M; Scherjon, S A

2005-01-01

Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

Perceptions of the roles of behaviour and genetics in disease risk: are they associated with behaviour change attempts.

PubMed

Nguyen, Anh B; Oh, April; Moser, Richard P; Patrick, Heather

2015-01-01

The aims of the present study were to (i) examine the prevalence of perceived behavioural and genetic causal beliefs for four chronic conditions (i.e. obesity, heart disease, diabetes and cancer); (ii) to examine the association between these causal beliefs and attempts at behaviour change (i.e. physical activity, weight management, fruit intake, vegetable intake and soda intake). The data come from the Health Information National Trends Survey, a nationally representative population-based survey of adults (N = 3407). Results indicated that participants held both behavioural and genetic causal beliefs for all four chronic conditions. Multivariate analyses indicated that behavioural causal beliefs were significantly associated with attempts to increase physical activity and vegetable intake and to decrease weight. Genetic causal beliefs for cancer were significantly associated with reported attempts to maintain weight. Behaviour and genetic causal beliefs were not associated with changes in either fruit or soda intake. In conclusion, while behavioural causal beliefs are associated with behavioural change, measurement must capture disease-specific behavioural causal beliefs as they are associated with different health behaviours.

Assessment of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk Factors of Heavy Metals in Autism.

PubMed

Mohamed, Farida El Baz; Zaky, Eman Ahmed; El-Sayed, Adel Bassuoni; Elhossieny, Reham Mohammed; Zahra, Sally Soliman; Salah Eldin, Waleed; Youssef, Walaa Yousef; Khaled, Rania Abdelmgeed; Youssef, Azza Mohamed

2015-01-01

The etiological factors involved in the etiology of autism remain elusive and controversial, but both genetic and environmental factors have been implicated. The aim of this study was to assess the levels and possible environmental risk factors and sources of exposure to mercury, lead, and aluminum in children with autism spectrum disorder (ASD) as compared to their matched controls. One hundred ASD children were studied in comparison to 100 controls. All participants were subjected to clinical evaluation and measurement of mercury, lead, and aluminum through hair analysis which reflects past exposure. The mean Levels of mercury, lead, and aluminum in hair of the autistic patients were significantly higher than controls. Mercury, lead, and aluminum levels were positively correlated with maternal fish consumptions, living nearby gasoline stations, and the usage of aluminum pans, respectively. Levels of mercury, lead, and aluminum in the hair of autistic children are higher than controls. Environmental exposure to these toxic heavy metals, at key times in development, may play a causal role in autism.

Update on Multiple Ovulations in Dairy Cattle.

PubMed

Macmillan, Kira; Kastelic, John P; Colazo, Marcos G

2018-04-24

This review updates the causal mechanisms and risk factors for multiple ovulations (MOV) in cattle. Clearly, MOV can lead to twin pregnancies, which negatively affects the health, production, and reproduction of cows. Therefore, a better understanding of the factors causing MOV may help to reduce twinning. Multiple ovulations occur after two or more follicles deviate and achieve codominance. The MOV rate is influenced by a complex network of hormones. For example, MOV is more common during periods of low progesterone (P4), that is, in anovulatory cattle or when luteolysis coincides with the selection of the future ovulatory follicle. There is also strong evidence for the luteinizing hormone (LH) being the primary factor leading to codominance, as high P4 concentrations suppress the transient LH surges and can reduce the ovulation rate in cattle or even inhibit deviation. Rates of MOV are increased in older and higher-producing dairy cows. Increased milk production and dry matter intake (DMI) increases hormone clearance, including P4; however, the association between milk yield and MOV has not been consistent. Additional risk factors for MOV include ovarian cysts, diet, season, and genetics.

Assessment of Hair Aluminum, Lead, and Mercury in a Sample of Autistic Egyptian Children: Environmental Risk Factors of Heavy Metals in Autism

PubMed Central

Mohamed, Farida El Baz; Zaky, Eman Ahmed; El-Sayed, Adel Bassuoni; Elhossieny, Reham Mohammed; Zahra, Sally Soliman; Salah Eldin, Waleed; Youssef, Walaa Yousef; Khaled, Rania Abdelmgeed; Youssef, Azza Mohamed

2015-01-01

Background and Aims. The etiological factors involved in the etiology of autism remain elusive and controversial, but both genetic and environmental factors have been implicated. The aim of this study was to assess the levels and possible environmental risk factors and sources of exposure to mercury, lead, and aluminum in children with autism spectrum disorder (ASD) as compared to their matched controls. Methods. One hundred ASD children were studied in comparison to 100 controls. All participants were subjected to clinical evaluation and measurement of mercury, lead, and aluminum through hair analysis which reflects past exposure. Results. The mean Levels of mercury, lead, and aluminum in hair of the autistic patients were significantly higher than controls. Mercury, lead, and aluminum levels were positively correlated with maternal fish consumptions, living nearby gasoline stations, and the usage of aluminum pans, respectively. Conclusion. Levels of mercury, lead, and aluminum in the hair of autistic children are higher than controls. Environmental exposure to these toxic heavy metals, at key times in development, may play a causal role in autism. PMID:26508811

Epilepsy surgery in context of neurocysticercosis

PubMed Central

Singh, Gagandeep; Chowdhary, Ashwani Kumar

2014-01-01

The association between neurocysticercosis (NCC) and epilepsy is well known and NCC is an important risk factor for epileptic seizures in many Taenia solium-endemic regions of the world. However, while the relationship between NCC and epilepsy is well known, the association between NCC and medically refractory (or surgically remediable epilepsy) has received little attention in the past. Our experience and review of the sparse literature available suggests that NCC is causally related to surgically remediable epilepsy albeit uncommonly so and that association derives its underpinnings from several different scenarios: (1) Medically refractory lesional epilepsy, in which seizures arise from the vicinity of the calcified neurocysticercus lesion (CNL), (2) Medically refractory epilepsy with dual pathology type of relationship between the hippocampal sclerosis (HS) and CNL in which both have been unequivocally demonstrated to give rise to independent seizures and (3) Mesial temporal lobe epilepsy due to HS with a distantly-located CNL, which is in itself not epileptogenic. A major point of controversy revolves around whether or not there exists a causal association between the CNL and HS. We believe that an association exists between NCC and HS and the most important factor influencing this association is the location of the CNL. Furthermore, NCC is a risk factor for medically-refractory epilepsy and that this might account for a considerable proportion of the intractable epilepsy population in endemic regions; the association has been largely ignored owing to the lack of availability of presurgical work-up facilities in these regions. Finally, from a clinical standpoint of presurgical evaluation, patients with CNL and HS should be evaluated on a case by case basis owing to disparate settings underlying the association. PMID:24791092

Fetal growth and risk of childhood asthma and allergic disease

PubMed Central

Tedner, S G; Örtqvist, A K; Almqvist, C

2012-01-01

Introduction Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods PubMed-search on pre-defined terms and cross-references. Results Several studies have shown a correlation between low birth weight and/or gestational age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subsequent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that diseases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases. PMID:22994341

Educational attainment and cigarette smoking: a causal association?†

PubMed Central

Gilman, Stephen E; Martin, Laurie T; Abrams, David B; Kawachi, Ichiro; Kubzansky, Laura; Loucks, Eric B; Rende, Richard; Rudd, Rima; Buka, Stephen L

2016-01-01

Background Despite abundant evidence that lower education is associated with a higher risk of smoking, whether the association is causal has not been convincingly established. Methods We investigated the association between education and lifetime smoking patterns in a birth cohort established in 1959 and followed through adulthood (n = 1311). We controlled for a wide range of potential confounders that were measured prior to school entry, and also estimated sibling fixed effects models to control for unmeasured familial vulnerability to smoking. Results In the full sample of participants, regression analyses adjusting for multiple childhood factors (including socioeconomic status, IQ, behavioural problems, and medical conditions) indicated that the number of pack-years smoked was higher among individuals with less than high school education [rate ratio (RR) = 1.58, confidence interval (CI) = 1.31, 1.91]. However, in the sibling fixed effects analysis the RR was 1.23 (CI = 0.80, 1.93). Similarly, adjusted models estimated in the full sample showed that individuals with less than high school education had fewer short-term (RR = 0.40; CI = 0.23, 0.69) and long-term (RR = 0.59; CI = 0.42, 0.83) quit attempts, and were less likely to quit smoking (odds ratio = 0.34; CI = 0.19, 0.62). The effects of education on quitting smoking were attenuated in the sibling fixed effects models that controlled for familial vulnerability to smoking. Conclusions A substantial portion of the education differential in smoking that has been repeatedly observed is attributable to factors shared by siblings that contribute to shortened educational careers and to lifetime smoking trajectories. Reducing disparities in cigarette smoking, including educational disparities, may therefore require approaches that focus on factors early in life that influence smoking risk over the adult life span. PMID:18180240

Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk

PubMed Central

Nguyen, Thu T.; Tchetgen Tchetgen, Eric J.; Kawachi, Ichiro; Gilman, Stephen E.; Walter, Stefan; Liu, Sze Y.; Manly, Jennifer; Glymour, M. Maria

2015-01-01

Purpose Education is an established correlate of cognitive status in older adulthood, but whether expanding educational opportunities would improve cognitive functioning remains unclear given limitations of prior studies for causal inference. Therefore, we conducted instrumental variable (IV) analyses of the association between education and dementia risk, using for the first time in this area, genetic variants as instruments as well as state-level school policies. Methods IV analyses in the Health and Retirement Study cohort (1998–2010) used two sets of instruments: 1) a genetic risk score constructed from three single nucleotide polymorphisms (SNPs) (n=8,054); and 2) compulsory schooling laws (CSLs) and state school characteristics (term length, student teacher ratios, and expenditures) (n=13,167). Results Employing the genetic risk score as an IV, there was a 1.1% reduction in dementia risk per year of schooling (95% CI: −2.4, 0.02). Leveraging compulsory schooling laws and state school characteristics as IVs, there was a substantially larger protective effect (−9.5%; 95% CI: −14.8, −4.2). Analyses evaluating the plausibility of the IV assumptions indicated estimates derived from analyses relying on CSLs provide the best estimates of the causal effect of education. Conclusion IV analyses suggest education is protective against risk of dementia in older adulthood. PMID:26633592

Causal Analysis of Self-tracked Time Series Data Using a Counterfactual Framework for N-of-1 Trials.

PubMed

Daza, Eric J

2018-02-01

Many of an individual's historically recorded personal measurements vary over time, thereby forming a time series (e.g., wearable-device data, self-tracked fitness or nutrition measurements, regularly monitored clinical events or chronic conditions). Statistical analyses of such n-of-1 (i.e., single-subject) observational studies (N1OSs) can be used to discover possible cause-effect relationships to then self-test in an n-of-1 randomized trial (N1RT). However, a principled way of determining how and when to interpret an N1OS association as a causal effect (e.g., as if randomization had occurred) is needed.Our goal in this paper is to help bridge the methodological gap between risk-factor discovery and N1RT testing by introducing a basic counterfactual framework for N1OS design and personalized causal analysis.We introduce and characterize what we call the average period treatment effect (APTE), i.e., the estimand of interest in an N1RT, and build an analytical framework around it that can accommodate autocorrelation and time trends in the outcome, effect carryover from previous treatment periods, and slow onset or decay of the effect. The APTE is loosely defined as a contrast (e.g., difference, ratio) of averages of potential outcomes the individual can theoretically experience under different treatment levels during a given treatment period. To illustrate the utility of our framework for APTE discovery and estimation, two common causal inference methods are specified within the N1OS context. We then apply the framework and methods to search for estimable and interpretable APTEs using six years of the author's self-tracked weight and exercise data, and report both the preliminary findings and the challenges we faced in conducting N1OS causal discovery.Causal analysis of an individual's time series data can be facilitated by an N1RT counterfactual framework. However, for inference to be valid, the veracity of certain key assumptions must be assessed critically, and the hypothesized causal models must be interpretable and meaningful. Schattauer GmbH.

Searching for an environmental effect of parental alcoholism on offspring alcohol use disorder: A genetically-informed study of children of alcoholics

PubMed Central

Slutske, Wendy S.; D’Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Harden, K. Paige; Heath, Andrew C.; Martin, Nicholas G.

2009-01-01

The children-of-twins design was used to isolate a potentially causal environmental impact of having an alcoholic parent on offspring alcohol use disorder by examining whether the children of alcoholics were at a higher risk for alcohol use disorders than the children of non-alcoholic parents even after correlated familial factors were controlled. Participants were 1,224 male and female twins from 836 twin pairs selected from the Australian Twin Registry, 2,334 of their 18–39 year-old offspring, and 983 spouses of the twins. Lifetime histories of DSM-IV alcohol use disorders were obtained by structured psychiatric telephone interviews conducted individually with each of the family members. Comparisons of the offspring of twins discordant for alcoholism indicated that there was no longer a statistically significant difference between the children of alcoholics and the children of non-alcoholics after genetic and family environmental factors correlated with having an alcoholic parent were controlled. The results of this study suggest that the direct causal effect of being exposed to an alcoholic parent on offspring alcohol use disorder is modest at best. PMID:18729607

Assessing the causal role of adiposity on disordered eating in childhood, adolescence, and adulthood: a Mendelian randomization analysis

PubMed Central

2017-01-01

Background: Observational studies have shown that higher body mass index (BMI) is associated with increased risk of developing disordered eating patterns. However, the causal direction of this relation remains ambiguous. Objective: We used Mendelian randomization (MR) to infer the direction of causality between BMI and disordered eating in childhood, adolescence, and adulthood. Design: MR analyses were conducted with a genetic score as an instrumental variable for BMI to assess the causal effect of BMI at age 7 y on disordered eating patterns at age 13 y with the use of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4473). To examine causality in the reverse direction, MR analyses were used to estimate the effect of the same disordered eating patterns at age 13 y on BMI at age 17 y via a split-sample approach in the ALSPAC. We also investigated the causal direction of the association between BMI and eating disorders (EDs) in adults via a two-sample MR approach and publically available genome-wide association study data. Results: MR results indicated that higher BMI at age 7 y likely causes higher levels of binge eating and overeating, weight and shape concerns, and weight-control behavior patterns in both males and females and food restriction in males at age 13 y. Furthermore, results suggested that higher levels of binge eating and overeating in males at age 13 y likely cause higher BMI at age 17 y. We showed no evidence of causality between BMI and EDs in adulthood in either direction. Conclusions: This study provides evidence to suggest a causal effect of higher BMI in childhood and increased risk of disordered eating at age 13 y. Furthermore, higher levels of binge eating and overeating may cause higher BMI in later life. These results encourage an exploration of the ways to break the causal chain between these complex phenotypes, which could inform and prevent disordered eating problems in adolescence. PMID:28747331

Assessing the causal role of adiposity on disordered eating in childhood, adolescence, and adulthood: a Mendelian randomization analysis.

PubMed

Reed, Zoe E; Micali, Nadia; Bulik, Cynthia M; Davey Smith, George; Wade, Kaitlin H

2017-09-01

Background: Observational studies have shown that higher body mass index (BMI) is associated with increased risk of developing disordered eating patterns. However, the causal direction of this relation remains ambiguous. Objective: We used Mendelian randomization (MR) to infer the direction of causality between BMI and disordered eating in childhood, adolescence, and adulthood. Design: MR analyses were conducted with a genetic score as an instrumental variable for BMI to assess the causal effect of BMI at age 7 y on disordered eating patterns at age 13 y with the use of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) ( n = 4473). To examine causality in the reverse direction, MR analyses were used to estimate the effect of the same disordered eating patterns at age 13 y on BMI at age 17 y via a split-sample approach in the ALSPAC. We also investigated the causal direction of the association between BMI and eating disorders (EDs) in adults via a two-sample MR approach and publically available genome-wide association study data. Results: MR results indicated that higher BMI at age 7 y likely causes higher levels of binge eating and overeating, weight and shape concerns, and weight-control behavior patterns in both males and females and food restriction in males at age 13 y. Furthermore, results suggested that higher levels of binge eating and overeating in males at age 13 y likely cause higher BMI at age 17 y. We showed no evidence of causality between BMI and EDs in adulthood in either direction. Conclusions: This study provides evidence to suggest a causal effect of higher BMI in childhood and increased risk of disordered eating at age 13 y. Furthermore, higher levels of binge eating and overeating may cause higher BMI in later life. These results encourage an exploration of the ways to break the causal chain between these complex phenotypes, which could inform and prevent disordered eating problems in adolescence.

Use of limited data to construct Bayesian networks for probabilistic risk assessment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groth, Katrina M.; Swiler, Laura Painton

2013-03-01

Probabilistic Risk Assessment (PRA) is a fundamental part of safety/quality assurance for nuclear power and nuclear weapons. Traditional PRA very effectively models complex hardware system risks using binary probabilistic models. However, traditional PRA models are not flexible enough to accommodate non-binary soft-causal factors, such as digital instrumentation&control, passive components, aging, common cause failure, and human errors. Bayesian Networks offer the opportunity to incorporate these risks into the PRA framework. This report describes the results of an early career LDRD project titled %E2%80%9CUse of Limited Data to Construct Bayesian Networks for Probabilistic Risk Assessment%E2%80%9D. The goal of the work was tomore » establish the capability to develop Bayesian Networks from sparse data, and to demonstrate this capability by producing a data-informed Bayesian Network for use in Human Reliability Analysis (HRA) as part of nuclear power plant Probabilistic Risk Assessment (PRA). This report summarizes the research goal and major products of the research.« less

Individual, physical and psychological risk factors for neck pain in Australian office workers: a 1-year longitudinal study

PubMed Central

Michaleff, Zoe; Maher, Christopher G.; Refshauge, Kathryn

2009-01-01

Neck pain is more prevalent in office workers than in the general community. To date, findings from prospective studies that investigated causal relationships between putative risk factors and the onset of neck pain in this population have been limited by high loss to follow-up. The aim of this research was to prospectively evaluate a range of risk factors for neck pain in office workers, using validated and reliable objective measures as well as attain an estimate of 1-year incidence. We assembled a cohort of 53 office workers without neck pain and measured individual, physical, workplace and psychological factors at baseline. We followed participants for 1 year to measure the incidence of neck pain. We achieved 100% participant follow-up. Cox regression analysis was applied to examine the relationship between the putative risk factors and the cumulative incidence of neck pain. The 1-year incidence proportion of neck pain in Australian office workers was estimated in this study to be 0.49 (95% CI 0.36–0.62). Predictors of neck pain with moderate to large effect sizes were female gender (HR: 3.07; 95% CI: 1.18–7.99) and high psychological stress (HR: 1.64; 95% CI: 0.66–4.07). Protective factors included increased mobility of the cervical spine (HR: 0.44; 95% CI: 0.19–1.05) and frequent exercise (HR: 0.64; 95% CI: 0.27–1.51). These results reveal that neck pain is common in Australian office workers and that there are risk factors that are potentially modifiable. PMID:19399537

Associations between film preferences and risk factors for suicide: an online survey.

PubMed

Till, Benedikt; Tran, Ulrich S; Voracek, Martin; Sonneck, Gernot; Niederkrotenthaler, Thomas

2014-01-01

Several studies indicate that exposure to suicide in movies is linked to subsequent imitative suicidal behavior, so-called copycat suicides, but little is currently known about whether the link between exposure to suicidal movies and suicidality is reflected in individual film preferences. 943 individuals participated in an online survey. We assessed associations between preferred film genres as well as individual exposure to and rating of 50 pre-selected films (including 25 featuring a suicide) with suicidal ideation, hopelessness, depression, life satisfaction, and psychoticism. Multiple regression analyses showed that preferences for film noir movies and milieu dramas were associated with higher scores on suicidal ideation, depression and psychoticism, and low scores on life satisfaction. Furthermore, preferences for thrillers and horror movies as well as preferences for tragicomedies, tragedies and melodramas were associated with higher scores of some of the suicide risk factors. There was also a dose-response relationship between positive rating of suicide films and higher life satisfaction. Due to the cross-sectional design of the study causality cannot be assessed. Individual film genre preferences seem to reflect risk factors of suicide, with film genres focusing on sad contents being preferred by individuals with higher scores on suicide risk factors. However, suicide movies are more enjoyed by viewers with higher life satisfaction, which may reflect a better ability to cope with such content.

Associations between Film Preferences and Risk Factors for Suicide: An Online Survey

PubMed Central

Till, Benedikt; Tran, Ulrich S.; Voracek, Martin; Sonneck, Gernot; Niederkrotenthaler, Thomas

2014-01-01

Several studies indicate that exposure to suicide in movies is linked to subsequent imitative suicidal behavior, so-called copycat suicides, but little is currently known about whether the link between exposure to suicidal movies and suicidality is reflected in individual film preferences. 943 individuals participated in an online survey. We assessed associations between preferred film genres as well as individual exposure to and rating of 50 pre-selected films (including 25 featuring a suicide) with suicidal ideation, hopelessness, depression, life satisfaction, and psychoticism. Multiple regression analyses showed that preferences for film noir movies and milieu dramas were associated with higher scores on suicidal ideation, depression and psychoticism, and low scores on life satisfaction. Furthermore, preferences for thrillers and horror movies as well as preferences for tragicomedies, tragedies and melodramas were associated with higher scores of some of the suicide risk factors. There was also a dose-response relationship between positive rating of suicide films and higher life satisfaction. Due to the cross-sectional design of the study causality cannot be assessed. Individual film genre preferences seem to reflect risk factors of suicide, with film genres focusing on sad contents being preferred by individuals with higher scores on suicide risk factors. However, suicide movies are more enjoyed by viewers with higher life satisfaction, which may reflect a better ability to cope with such content. PMID:25028966

Association between sugar-sweetened and artificially sweetened soft drinks and type 2 diabetes: systematic review and dose-response meta-analysis of prospective studies.

PubMed

Greenwood, D C; Threapleton, D E; Evans, C E L; Cleghorn, C L; Nykjaer, C; Woodhead, C; Burley, V J

2014-09-14

The intake of sugar-sweetened soft drinks has been reported to be associated with an increased risk of type 2 diabetes, but it is unclear whether this is because of the sugar content or related lifestyle factors, whether similar associations hold for artificially sweetened soft drinks, and how these associations are related to BMI. We aimed to conduct a systematic literature review and dose-response meta-analysis of evidence from prospective cohorts to explore these issues. We searched multiple sources for prospective studies on sugar-sweetened and artificially sweetened soft drinks in relation to the risk of type 2 diabetes. Data were extracted from eleven publications on nine cohorts. Consumption values were converted to ml/d, permitting the exploration of linear and non-linear dose-response trends. Summary relative risks (RR) were estimated using a random-effects meta-analysis. The summary RR for sugar-sweetened and artificially sweetened soft drinks were 1·20/330 ml per d (95 % CI 1·12, 1·29, P< 0·001) and 1·13/330 ml per d (95 % CI 1·02, 1·25, P= 0·02), respectively. The association with sugar-sweetened soft drinks was slightly lower in studies adjusting for BMI, consistent with BMI being involved in the causal pathway. There was no evidence of effect modification, though both these comparisons lacked power. Overall between-study heterogeneity was high. The included studies were observational, so their results should be interpreted cautiously, but findings indicate a positive association between sugar-sweetened soft drink intake and type 2 diabetes risk, attenuated by adjustment for BMI. The trend was less consistent for artificially sweetened soft drinks. This may indicate an alternative explanation, such as lifestyle factors or reverse causality. Future research should focus on the temporal nature of the association and whether BMI modifies or mediates the association.

Associations Between Divorce and Onset of Drug Abuse in a Swedish National Sample.

PubMed

Edwards, Alexis C; Larsson Lönn, Sara; Sundquist, Jan; Kendler, Kenneth S; Sundquist, Kristina

2018-05-01

Rates of drug abuse are higher among divorced individuals than among those who are married, but it is not clear whether divorce itself is a risk factor for drug abuse or whether the observed association is confounded by other factors. We examined the association between divorce and onset of drug abuse in a population-based Swedish cohort born during 1965-1975 (n = 651,092) using Cox proportional hazards methods, with marital status as a time-varying covariate. Potential confounders (e.g., demographics, adolescent deviance, and family history of drug abuse) were included as covariates. Parallel analyses were conducted for widowhood and drug-abuse onset. In models with adjustments, divorce was associated with a substantial increase in risk of drug-abuse onset in both sexes (hazard ratios > 5). Co-relative analyses (among biological relatives) were consistent with a partially causal role of divorce on drug-abuse onset. Widowhood also increased risk of drug-abuse onset, although to a lesser extent. Divorce is a potent risk factor for onset of drug abuse, even after adjusting for deviant behavior in adolescence and family history of drug abuse. The somewhat less-pronounced association with widowhood, particularly among men, suggests that the magnitude of association between divorce and drug abuse may not be generalizable to the end of a relationship.

Identifying causal linkages between environmental variables and African conflicts

NASA Astrophysics Data System (ADS)

Nguy-Robertson, A. L.; Dartevelle, S.

2017-12-01

Environmental variables that contribute to droughts, flooding, and other natural hazards are often identified as factors contributing to conflict; however, few studies attempt to quantify these causal linkages. Recent research has demonstrated that the environment operates within a dynamical system framework and the influence of variables can be identified from convergent cross mapping (CCM) between shadow manifolds. We propose to use CCM to identify causal linkages between environmental variables and incidences of conflict. This study utilizes time series data from Climate Forecast System ver. 2 and MODIS satellite sensors processed using Google Earth Engine to aggregate country and regional trends. These variables are then compared to Armed Conflict Location & Event Data Project observations at similar scales. Results provide relative rankings of variables and their linkage to conflict. Being able to identify which factors contributed more strongly to a conflict can allow policy makers to prepare solutions to mitigate future crises. Knowledge of the primary environmental factors can lead to the identification of other variables to examine in the causal network influencing conflict.

Modeling drivers of phosphorus loads in Chesapeake Bay tributaries and inferences about long-term change

USGS Publications Warehouse

Ryberg, Karen R.; Blomquist, Joel; Sprague, Lori A.; Sekellick, Andrew J.; Keisman, Jennifer

2018-01-01

Causal attribution of changes in water quality often consists of correlation, qualitative reasoning, listing references to the work of others, or speculation. To better support statements of attribution for water-quality trends, structural equation modeling was used to model the causal factors of total phosphorus loads in the Chesapeake Bay watershed. By transforming, scaling, and standardizing variables, grouping similar sites, grouping some causal factors into latent variable models, and using methods that correct for assumption violations, we developed a structural equation model to show how causal factors interact to produce total phosphorus loads. Climate (in the form of annual total precipitation and the Palmer Hydrologic Drought Index) and anthropogenic inputs are the major drivers of total phosphorus load in the Chesapeake Bay watershed. Increasing runoff due to natural climate variability is offsetting purposeful management actions that are otherwise decreasing phosphorus loading; consequently, management actions may need to be reexamined to achieve target reductions in the face of climate variability.

Environmental Risk Factors for Multiple Sclerosis: A Review with a Focus on Molecular Mechanisms

PubMed Central

O’Gorman, Cullen; Lucas, Robyn; Taylor, Bruce

2012-01-01

Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system commonly affecting young adults. Pathologically, there are patches of inflammation (plaques) with demyelination of axons and oligodendrocyte loss. There is a global latitude gradient in MS prevalence, and incidence of MS is increasing (particularly in females). These changes suggest a major role for environmental factors in causation of disease. We have reviewed the evidence and potential mechanisms of action for three exposures: vitamin D, Epstein Barr virus and cigarette smoking. Recent advances supporting gene-environment interactions are reviewed. Further research is needed to establish mechanisms of causality in humans and to explore preventative strategies. PMID:23109880

Role of Ureaplasma Respiratory Tract Colonization in Bronchopulmonary Dysplasia Pathogenesis: Current Concepts and Update.

PubMed

Viscardi, Rose Marie; Kallapur, Suhas G

2015-12-01

Respiratory tract colonization with the genital mycoplasma species Ureaplasma parvum and Ureaplasma urealyticum in preterm infants is a significant risk factor for bronchopulmonary dysplasia (BPD). Recent studies of the ureaplasmal genome, animal infection models, and human infants have provided a better understanding of specific virulence factors, pathogen-host interactions, and variability in genetic susceptibility that contribute to chronic infection, inflammation, and altered lung development. This review provides an update on the current evidence supporting a causal role of ureaplasma infection in BPD pathogenesis. The current status of antibiotic trials to prevent BPD in Ureaplasma-infected preterm infants is also reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

Breast Cancer in Australian Indigenous Women: Incidence, Mortality, and Risk Factors

PubMed Central

Tapia, Kriscia A; Garvey, Gail; Entee, Mark Mc; Rickard, Mary; Brennan, Patrick

2017-01-01

The Indigenous people of Australia face significant health gaps compared with the general population, with lower life expectancies, higher rates of death, and chronic illness occurring more often than in non-indigenous Australians. Cancer is the second largest contributor to the burden of disease with breast cancer being the most common invasive cancer diagnosed for females. Despite a lower breast cancer incidence compared with non-indigenous women, fatalities occur at an elevated rate and breast cancers have an earlier age of onset. For indigenous women there are also more advanced and distant tumours at diagnosis, fewer hospitalisations for breast cancer, and lower participation in breast screening. Concomitantly there are demographic, socio-economic and lifestyle factors associated with breast cancer risks that are heavily represented within Indigenous communities. The aim of this two-part narrative review is to examine the available evidence on breast cancer and its risk factors in Australian Indigenous women. Part One presents a summary of the latest incidence, survival and mortality data. Part Two presents the risk factors most strongly associated with breast cancer including age, place of residence, family risk, genetics, reproductive history, tobacco use, alcohol intake, physical activity, participation in screening and breast density. With increasing emphasis on personalized health care, a clear understanding of breast cancer incidence, survival, mortality, and causal agents within the Indigenous population is required if breast cancer prevention and management is to be optimized for Indigenous Australians. PMID:28545182

"Head take you": causal attributions of mental illness in Jamaica.

PubMed

Arthur, Carlotta M; Whitley, Rob

2015-02-01

Causal attributions are a key factor in explanatory models of illness; however, little research on causal attributions of mental illness has been conducted in developing nations in the Caribbean, including Jamaica. Explanatory models of mental illness may be important in understanding illness experience and be a crucial factor in mental health service seeking and utilization. We explored causal attributions of mental illness in Jamaica by conducting 20 focus groups, including 16 community samples, 2 patient samples, and 2 samples of caregivers of patients, with a total of 159 participants. The 5 most commonly endorsed causal attributions of mental illness are discussed: (a) drug-related causes, including ganja (marijuana); (b) biological causes, such as chemical imbalance, familial transmission, and "blood"; (c) psychological causes, including stress and thinking too much; (d) social causes, such as relationship problems and job loss; and (e) spiritual or religious causes, including Obeah. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Causal Factors Influencing Adversity Quotient of Twelfth Grade and Third-Year Vocational Students

ERIC Educational Resources Information Center

Pangma, Rachapoom; Tayraukham, Sombat; Nuangchalerm, Prasart

2009-01-01

Problem statement: The aim of this research was to study the causal factors influencing students' adversity between twelfth grade and third-year vocational students in Sisaket province, Thailand. Six hundred and seventy two of twelfth grade and 376 third-year vocational students were selected by multi-stage random sampling techniques. Approach:…

Biochemical and molecular mechanisms for the association between obesity, chronic inflammation, and breast cancer.

PubMed

Rose, David P; Vona-Davis, Linda

2014-01-01

Upper body obesity is a risk factor for postmenopausal breast cancer and is related to an aggressive tumor phenotype and a poor prognosis regardless of menopausal status. After the menopause, the major mechanism for the association with disease risk is elevated estrogen production by adipose tissue, due to a high level of aromatase activity: these hormone-dependent tumors express both estrogen and progesterone receptors. Other important biological factors of risk include leptin and adiponectin, adipokines with opposing endocrine and paracrine activities, and obesity-related hyperinsulinemia. Chronic inflammation of the breast adipose tissue, which occurs in some obese women and is indicated by the accumulation of macrophages around dead adipocytes ("crown-like structures"), rather than adiposity per se, may prove to be the pathological lesion responsible for both local aromatase induction, and enhanced invasiveness and metastatic capacity through biological mechanisms that involve leptin, tumor necrosis factor-α, and insulin. A causal association between obesity in premenopausal women and breast cell epithelial-mesenchymal transition, perhaps with the participation of the Wnt signaling pathway, and aggressive hormone-independent breast cancer is suggested by a number of experimental and clinical studies. © 2013 International Union of Biochemistry and Molecular Biology.

Prevalence of traumatic brain injury in intimate partner violence offenders compared to the general population: a meta-analysis.

PubMed

Farrer, Thomas J; Frost, R Brock; Hedges, Dawson W

2012-04-01

Intimate partner violence (IPV) is widespread. Several risk factors are associated with IPV perpetuation, including alcohol use and educational level. The aggression and violence associated with traumatic brain injury (TBI) suggest that brain trauma may also be a risk factor for IPV. To examine the association between TBI and IPV, the authors conducted a meta-analysis of peer-reviewed published studies reporting the prevalence of TBI in IPV perpetrators. The authors compared the frequency of TBI among IPV perpetuators to estimates of TBI in the general population using a single-sample test of proportions. Six studies containing a total of 222 subjects met inclusion criteria. Fifty-three percent (119) of the IPV perpetuators had a history of TBI, a prevalence significantly higher (p < .0001) than estimates of TBI in the general population. The prevalence of TBI among perpetuators of IPV appears significantly higher than the prevalence of TBI in the general population. To the extent that this association is causal, TBI may be a risk factor for interpersonal violence, although comparatively few source studies, lack of standardized information about TBI severity, and the inability to investigate potential confounding variables necessarily limit this conclusion.

The relationship between neuroticism, major depressive disorder and comorbid disorders in Chinese women

PubMed Central

Xia, Jing; He, Qiang; Li, Yihan; Xie, Dong; Zhu, Suoyu; Chen, Jing; Shen, Yuan; Zhang, Ning; Wei, Yan; Chen, Chunfeng; Shen, Jianhua; Zhang, Yan; Gao, Chengge; Li, Youhui; Ding, Jihong; Shen, Wenwu; Wang, Qian; Cao, Meiyue; Liu, Tiebang; Zhang, Jinbei; Duan, Huijun; Bao, Cheng; Ma, Ping; Zhou, Cong; Luo, Yanfang; Zhang, Fengzhi; Liu, Ying; Li, Yi; Jin, Guixing; Zhang, Yutang; Liang, Wei; Chen, Yunchun; Zhao, Changyin; Li, Haiyan; Chen, Yiping; Shi, Shenxun; Kendler, Kenneth S.; Flint, Jonathan; Wang, Xumei

2011-01-01

Objective The personality trait of neuroticism is a risk factor for major depressive disorder (MDD), but this relationship has not been demonstrated in clinical samples from Asia. Methods We examined a large-scale clinical study of Chinese Han women with recurrent major depression and community-acquired controls. Results Elevated levels of neuroticism increased the risk for lifetime MDD (with an odds ratio of 1.37 per SD), contributed to the comorbidity of MDD with anxiety disorders, and predicted the onset and severity of MDD. Our findings largely replicate those obtained in clinical populations in Europe and US but differ in two ways: we did not find a relationship between melancholia and neuroticism; we found lower mean scores for neuroticism (3.6 in our community control sample). Limitations Our findings do not apply to MDD in community-acquired samples and may be limited to Han Chinese women. It is not possible to determine whether the association between neuroticism and MDD reflects a causal relationship. Conclusions Neuroticism acts as a risk factor for MDD in Chinese women, as it does in the West and may particularly predispose to comorbidity with anxiety disorders. Cultural factors may have an important effect on its measurement. PMID:21824661

[Pharmacovigilance of hepatitis B vaccines].

PubMed

Imbs, Jean-Louis; Decker, Nicole; Welsch, Marie

2003-01-01

Since the hepatitis B vaccine are on the market in France, until the end of 2002, 1211 observations of demyelinating disease of the central nervous system (1109 cases of which 895 multiple sclerosis) or peripheral (102 cases of which 49 Guillain Barre Syndrome), have been reported to the french network of pharmacovigilance and to the AFSSAPS. It is not possible to singularize these observations, neither from a clinical nor an epidemiological point of view. No risk factor has been detected. Only the chronology could suggest a causal relationship, the vaccine preceding the pathology in all the cases notified.

Epidemiological Interpretation of Studies Examining the Effect of Antibiotic Usage on Resistance

PubMed Central

Schechner, Vered; Temkin, Elizabeth; Harbarth, Stephan; Carmeli, Yehuda

2013-01-01

SUMMARY Bacterial resistance to antibiotics is a growing clinical problem and public health threat. Antibiotic use is a known risk factor for the emergence of antibiotic resistance, but demonstrating the causal link between antibiotic use and resistance is challenging. This review describes different study designs for assessing the association between antibiotic use and resistance and discusses strengths and limitations of each. Approaches to measuring antibiotic use and antibiotic resistance are presented. Important methodological issues such as confounding, establishing temporality, and control group selection are examined. PMID:23554418

Formulating and Answering High-Impact Causal Questions in Physiologic Childbirth Science: Concepts and Assumptions.

PubMed

Snowden, Jonathan M; Tilden, Ellen L; Odden, Michelle C

2018-06-08

In this article, we conclude our 3-part series by focusing on several concepts that have proven useful for formulating causal questions and inferring causal effects. The process of causal inference is of key importance for physiologic childbirth science, so each concept is grounded in content related to women at low risk for perinatal complications. A prerequisite to causal inference is determining that the question of interest is causal rather than descriptive or predictive. Another critical step in defining a high-impact causal question is assessing the state of existing research for evidence of causality. We introduce 2 causal frameworks that are useful for this undertaking, Hill's causal considerations and the sufficient-component cause model. We then provide 3 steps to aid perinatal researchers in inferring causal effects in a given study. First, the researcher should formulate a rigorous and clear causal question. We introduce an example of epidural analgesia and labor progression to demonstrate this process, including the central role of temporality. Next, the researcher should assess the suitability of the given data set to answer this causal question. In randomized controlled trials, data are collected with the express purpose of answering the causal question. Investigators using observational data should also ensure that their chosen causal question is answerable with the available data. Finally, investigators should design an analysis plan that targets the causal question of interest. Some data structures (eg, time-dependent confounding by labor progress when estimating the effect of epidural analgesia on postpartum hemorrhage) require specific analytical tools to control for bias and estimate causal effects. The assumptions of consistency, exchangeability, and positivity may be especially useful in carrying out these steps. Drawing on appropriate causal concepts and considering relevant assumptions strengthens our confidence that research has reduced the likelihood of alternative explanations (eg bias, chance) and estimated a causal effect. © 2018 by the American College of Nurse-Midwives.

Gene-environment interaction in atopic diseases: a population-based twin study of early-life exposures.

PubMed

Kahr, Niklas; Naeser, Vibeke; Stensballe, Lone Graff; Kyvik, Kirsten Ohm; Skytthe, Axel; Backer, Vibeke; Bønnelykke, Klaus; Thomsen, Simon Francis

2015-01-01

The development of atopic diseases early in life suggests an important role of perinatal risk factors. To study whether early-life exposures modify the genetic influence on atopic diseases in a twin population. Questionnaire data on atopic diseases from 850 monozygotic and 2279 like-sex dizygotic twin pairs, 3-9 years of age, from the Danish Twin Registry were cross-linked with data on prematurity, Cesarean section, maternal age at birth, parental cohabitation, season of birth and maternal smoking during pregnancy, from the Danish National Birth Registry. Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis. After multivariable adjustment, prematurity (gestational age below 32 weeks) [odds ratio (OR) = 1.93, confidence interval (CI) = 1.45-2.56], Cesarean section (OR = 1.25, CI = 1.05-1.49) and maternal smoking during pregnancy (OR = 1.70, CI = 1.42-2.04) significantly influenced the risk of asthma, whereas none of the factors were significantly associated with atopic dermatitis and hay fever. Variance components analysis stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors. In this population-based study of children, there was no evidence of genetic effect modification of atopic diseases by several identified early-life risk factors. The causal relationship between these risk factors and atopic diseases may therefore be mediated via mechanisms different from gene-environment interaction. © 2014 John Wiley & Sons Ltd.

A cross-sectional study of the relationship between job demand-control, effort-reward imbalance and cardiovascular heart disease risk factors

PubMed Central

2012-01-01

Background This cross-sectional study explored relationships between psychosocial work environment, captured by job demand-control (JDC) and effort-reward imbalance (ERI), and seven cardiovascular heart disease (CHD) risk factors in a general population. Method The sampled consists of randomly-selected men and women from Gothenburg, Sweden and the city’s surrounding metropolitan areas. Associations between psychosocial variables and biomarkers were analysed with multiple linear regression adjusted for age, smoking, education and occupational status. Results The study included 638 men and 668 women aged 24–71. Analysis between JDC and CHD risk factors illustrated that, for men, JDC was associated with impaired scores in several biomarkers, especially among those in high strain jobs. For women, there were no relationships between JDC and biomarkers. In the analysis of links between ERI and CHD risk factors, most associations tested null. The only findings were raised triglycerides and BMI among men in the fourth quartile of the ERI-ratio distribution, and lowered LDL-cholesterol for women. An complementary ERI analysis, combining high/low effort and reward into categories, illustrated lowered triglycerides and elevated HDL-cholesterol values among women reporting high efforts and high rewards, compared to women experiencing low effort and high reward. Conclusions There were some associations between psychosocial stressors and CHD risk factors. The cross-sectional design did not allow conclusions about causality but some results indicated gender differences regarding sensitivity to work stressors and also how the models might capture different psychosocial dimensions. PMID:23259757

The impact of a private sector living wage intervention on consumption and cardiovascular disease risk factors in a middle income country.

PubMed

Rehkopf, David H; Burmaster, Katharine; Landefeld, John C; Adler-Milstein, Sarah; Flynn, Emily P; Acevedo, Maria Cecilia; Jones-Smith, Jessica C; Adler, Nancy; Fernald, Lia C H

2018-01-25

A positive association of socioeconomic position and health is well established in high-income countries. In poorer nations, however, higher income individuals often have more cardiovascular risk factors (including obesity) than do those with less income. Our study goal was to estimate the effects of receiving a living wage (340% higher income) on short-term changes in consumption and cardiovascular risk factors among low-wage workers in a middle-income country. This cross-sectional study matched workers at an apparel factory (n=105) in the Dominican Republic with those at a similar factory (n=99) nearby, 15 months after the intervention factory introduced a substantially higher living wage. Statistical matching on non-time varying individual characteristics (childhood health, childhood living conditions, work experience, demographic factors) strengthened causal inference. Primary outcomes were blood pressure (systolic and diastolic), pulse rate, body mass index and waist circumference. Secondary outcomes were dietary consumption and spending on services, consumables and durable goods. Receiving the living wage was associated with increased consumption of protein, dairy, soda and juice and sugars, but not with cardiovascular risk factors. Intervention factory workers spent more on grocery items and household durable goods. While having a higher income in a middle-income country might be expected to increase obesity and its associated health risks, the current study found no short-term negative associations. There may be possible longer-term negative health consequences of increases in consumption of soda, juice and sugars, however. It is important to consider complementary interventions to support healthy dietary intake in areas with increasing wages.

Gene-environment interaction study for BMI reveals interactions between genetic factors and physical activity, alcohol consumption and socioeconomic status

PubMed Central

Karlsson, Torgny; Ek, Weronica E.

2017-01-01

Previous genome-wide association studies (GWAS) have identified hundreds of genetic loci to be associated with body mass index (BMI) and risk of obesity. Genetic effects can differ between individuals depending on lifestyle or environmental factors due to gene-environment interactions. In this study, we examine gene-environment interactions in 362,496 unrelated participants with Caucasian ancestry from the UK Biobank resource. A total of 94 BMI-associated SNPs, selected from a previous GWAS on BMI, were used to construct weighted genetic scores for BMI (GSBMI). Linear regression modeling was used to estimate the effect of gene-environment interactions on BMI for 131 lifestyle factors related to: dietary habits, smoking and alcohol consumption, physical activity, socioeconomic status, mental health, sleeping patterns, as well as female-specific factors such as menopause and childbirth. In total, 15 lifestyle factors were observed to interact with GSBMI, of which alcohol intake frequency, usual walking pace, and Townsend deprivation index, a measure of socioeconomic status, were all highly significant (p = 1.45*10−29, p = 3.83*10−26, p = 4.66*10−11, respectively). Interestingly, the frequency of alcohol consumption, rather than the total weekly amount resulted in a significant interaction. The FTO locus was the strongest single locus interacting with any of the lifestyle factors. However, 13 significant interactions were also observed after omitting the FTO locus from the genetic score. Our analyses indicate that many lifestyle factors modify the genetic effects on BMI with some groups of individuals having more than double the effect of the genetic score. However, the underlying causal mechanisms of gene-environmental interactions are difficult to deduce from cross-sectional data alone and controlled experiments are required to fully characterise the causal factors. PMID:28873402

Effect of interpregnancy interval on risk of spontaneous preterm birth in Emirati women, United Arab Emirates.

PubMed Central

Al-Jasmi, Fatima; Al-Mansoor, Fatima; Alsheiba, Aisha; Carter, Anne O.; Carter, Thomas P.; Hossain, M. Moshaddeque

2002-01-01

OBJECTIVE: To investigate whether a short interpregnancy interval is a risk factor for preterm birth in Emirati women, where there is a wide range of interpregnancy intervals and uniformity in potentially confounding factors. METHODS: A case-control design based on medical records was used. A case was defined as a healthy multiparous Emirati woman delivering a healthy singleton spontaneously before 37 weeks of gestation between 1997 and 2000, and a control was defined as the next eligible similar woman delivering after 37 weeks of gestation. Women were excluded if there was no information available about their most recent previous pregnancy or if it had resulted in a multiple or preterm birth. Data collected from charts and delivery room records were analysed using the STATA statistical package. All variables found to be valid, stable and significant by univariate analysis were included in multivariate logistic regression analysis. FINDINGS: There were 128 cases who met the eligibility criteria; 128 controls were selected. Short interpregnancy intervals were significantly associated with case status (P<0.05). The multivariate adjusted odds ratios for the 1st, 2nd, and 4th quartiles of interpregnancy interval compared with the lowest-risk 3rd quartile were 8.2, 5.4, and 2.0 (95% confidence intervals: 3.5-19.2, 2.4-12.6, and 0.9- 4.5 respectively). CONCLUSION: A short interpregnancy interval is a risk factor for spontaneous preterm birth in Emirati women. The magnitude of the risk and the risk gradient between exposure quartiles suggest that the risk factor is causal and that its modification would reduce the risk of preterm birth. PMID:12481208

The association between tobacco and the risk of asthma, rhinoconjunctivitis and eczema in children and adolescents: analyses from Phase Three of the ISAAC programme.

PubMed

Mitchell, Edwin A; Beasley, Richard; Keil, Ulrich; Montefort, Stephen; Odhiambo, Joseph

2012-11-01

Exposure to parental smoking is associated with wheeze in early childhood, but in 2006 the US Surgeon General stated that the evidence is insufficient to infer a causal relationship between exposure and asthma in childhood and adolescents. To examine the association between maternal and paternal smoking and symptoms of asthma, eczema and rhinoconjunctivitis. Parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis and eczema, and several risk factors, including maternal smoking in the child's first year of life, current maternal smoking (and amount) and paternal smoking. Adolescents aged 13-14 years self completed the questionnaires on these symptoms and whether their parents currently smoked. In the 6-7-year age group there were 220 407 children from 75 centres in 32 countries. In the 13-14-year age group there were 350 654 adolescents from 118 centres in 53 countries. Maternal and paternal smoking was associated with an increased risk of symptoms of asthma, eczema and rhinoconjunctivitis in both age groups, although the magnitude of the OR is higher for symptoms of asthma than the other outcomes. Maternal smoking is associated with higher ORs than paternal smoking. For asthma symptoms there is a clear dose relationship (1-9 cigarettes/day, OR 1.27; 10-19 cigarettes/day, OR 1.35; and 20+ cigarettes/day, OR 1.56). When maternal smoking in the child's first year of life and current maternal smoking are considered, the main effect is due to maternal smoking in the child's first year of life. There was no interaction between maternal and paternal smoking. This study has confirmed the importance of maternal smoking, and the separate and additional effect of paternal smoking. The presence of a dose-response effect relationship with asthma symptoms suggests that the relationship is causal, however for eczema and rhinoconjunctivitis causality is less certain.

Job demands and job strain as risk factors for employee wellbeing in elderly care: an instrumental-variables analysis.

PubMed

Elovainio, Marko; Heponiemi, Tarja; Kuusio, Hannamaria; Jokela, Markus; Aalto, Anna-Mari; Pekkarinen, Laura; Noro, Anja; Finne-Soveri, Harriet; Kivimäki, Mika; Sinervo, Timo

2015-02-01

The association between psychosocial work environment and employee wellbeing has repeatedly been shown. However, as environmental evaluations have typically been self-reported, the observed associations may be attributable to reporting bias. Applying instrumental-variable regression, we used staffing level (the ratio of staff to residents) as an unconfounded instrument for self-reported job demands and job strain to predict various indicators of wellbeing (perceived stress, psychological distress and sleeping problems) among 1525 registered nurses, practical nurses and nursing assistants working in elderly care wards. In ordinary regression, higher self-reported job demands and job strain were associated with increased risk of perceived stress, psychological distress and sleeping problems. The effect estimates for the associations of these psychosocial factors with perceived stress and psychological distress were greater, but less precisely estimated, in an instrumental-variables analysis which took into account only the variation in self-reported job demands and job strain that was explained by staffing level. No association between psychosocial factors and sleeping problems was observed with the instrumental-variable analysis. These results support a causal interpretation of high self-reported job demands and job strain being risk factors for employee wellbeing. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Local bladder cancer clusters in southeastern Michigan accounting for risk factors, covariates and residential mobility.

PubMed

Jacquez, Geoffrey M; Shi, Chen; Meliker, Jaymie R

2015-01-01

In case control studies disease risk not explained by the significant risk factors is the unexplained risk. Considering unexplained risk for specific populations, places and times can reveal the signature of unidentified risk factors and risk factors not fully accounted for in the case-control study. This potentially can lead to new hypotheses regarding disease causation. Global, local and focused Q-statistics are applied to data from a population-based case-control study of 11 southeast Michigan counties. Analyses were conducted using both year- and age-based measures of time. The analyses were adjusted for arsenic exposure, education, smoking, family history of bladder cancer, occupational exposure to bladder cancer carcinogens, age, gender, and race. Significant global clustering of cases was not found. Such a finding would indicate large-scale clustering of cases relative to controls through time. However, highly significant local clusters were found in Ingham County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The Jackson City cluster was observed in working-ages and is thus consistent with occupational causes. The Ingham County cluster persists over time, suggesting a broad-based geographically defined exposure. Focused clusters were found for 20 industrial sites engaged in manufacturing activities associated with known or suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple testing were not significant, although local clusters persisted through time and temporal trends in probability of local tests were observed. Q analyses provide a powerful tool for unpacking unexplained disease risk from case-control studies. This is particularly useful when the effect of risk factors varies spatially, through time, or through both space and time. For bladder cancer in Michigan, the next step is to investigate causal hypotheses that may explain the excess bladder cancer risk localized to areas of Oakland and Ingham counties, and to the City of Jackson.

Predicting the unpredictable? Identifying high-risk versus low-risk parents with intellectual disabilities.

PubMed

McGaw, Sue; Scully, Tamara; Pritchard, Colin

2010-09-01

This study set out to identify risk factors affecting parents with intellectual disabilities (IDs) by determining: (i) whether perception of family support differs between parents with IDs, referring professionals, and a specialist parenting service; (ii) whether multivariate familial and demographic factors differentiates 'high-risk' from 'low-risk' parenting; and (iii) the impact of partner relationships on parental competency and risk status. Secondary data analysis was conducted on data gathered from 101 parents with IDs and 172 of their children, all of whom had been referred to a specialist parenting service over a 5 year period. Cross-tabulations were applied to the data to examine causal processes and to improve general understanding of the risks associated with families. Contrary to popular expectations IQ levels of the main parent, relationship status, parental age, employment, amenities, valued support and parents' perception of need were not identified as contributory factors distinguishing 'high-risk' from 'low-risk' parents. Instead, 'high-risk' parenting associated more with parental reports of childhood trauma (emotional abuse and physical neglect in particular), parents' having additional special needs in addition to their IDs or parents who were raising a child with special needs. Other 'high-risk' factors identified related to the male partners of mothers with IDs, many of whom did not have IDs and/or whose histories included anti-social behaviors or criminality. The study identified some high-risk variables among parents with IDs that can distinguish them from low-risk parents with IDs. These findings generate challenges for agencies who attempt to capture the needs of parents with IDs and who endeavour to provide services to families deemed to be "at risk." These outcomes will be of special interest to the courts, especially when parents with IDs are involved in care proceedings. Copyright © 2010. Published by Elsevier Ltd.

Controversies about a common etiology for eating and mood disorders

PubMed Central

Rossetti, Clara; Halfon, Olivier; Boutrel, Benjamin

2014-01-01

Obesity and depression represent a growing health concern worldwide. For many years, basic science and medicine have considered obesity as a metabolic illness, while depression was classified a psychiatric disorder. Despite accumulating evidence suggesting that obesity and depression may share commonalities, the causal link between eating and mood disorders remains to be fully understood. This etiology is highly complex, consisting of multiple environmental and genetic risk factors that interact with each other. In this review, we sought to summarize the preclinical and clinical evidence supporting a common etiology for eating and mood disorders, with a particular emphasis on signaling pathways involved in the maintenance of energy balance and mood stability, among which orexigenic and anorexigenic neuropeptides, metabolic factors, stress responsive hormones, cytokines, and neurotrophic factors. PMID:25386150

[Dialogues on risks and health resources in general practice].

PubMed

Hollnagel, Hanne; Malterud, Kirsti

2002-11-04

The healing and preventive forces related to individuals' health resources and self-assessed knowledge have hitherto been underestimated in medicine. In this article, we draw attention to ethical and epistemological challenges in relation to values, communication, knowledge, and autonomy that are embedded in the prevailing risk-oriented epidemiology. We have developed a theoretical model for a patient-centered, salutogenetic approach with the aim of a better balance between health resources and risk factors. We briefly present results of dialogues in the general practice consultation based on key questions about self-assessed health resources. We discuss pitfalls related to causality, group-based probabilities, medicalization, and informed consent, focusing on the clinical encounter with the individual patient. By introducing a salutogenetic perspective, we hope to shift attention towards the patient's resources and strengths. Communication can mediate oppression as well as empowerment.

A Longitudinal Analysis of the Causal Factors in Major Maritime Accidents in the USA and Canada (1996-2006)

NASA Technical Reports Server (NTRS)

Johnson, C. W.; Holloway, C, M.

2007-01-01

Accident reports provide important insights into the causes and contributory factors leading to particular adverse events. In contrast, this paper provides an analysis that extends across the findings presented over ten years investigations into maritime accidents by both the US National Transportation Safety Board (NTSB) and Canadian Transportation Safety Board (TSB). The purpose of the study was to assess the comparative frequency of a range of causal factors in the reporting of adverse events. In order to communicate our findings, we introduce J-H graphs as a means of representing the proportion of causes and contributory factors associated with human error, equipment failure and other high level classifications in longitudinal studies of accident reports. Our results suggest the proportion of causal and contributory factors attributable to direct human error may be very much smaller than has been suggested elsewhere in the human factors literature. In contrast, more attention should be paid to wider systemic issues, including the managerial and regulatory context of maritime operations.

Trans-ethnic follow-up of breast cancer GWAS hits using the preferential linkage disequilibrium approach

PubMed Central

Zhu, Qianqian; Shepherd, Lori; Lunetta, Kathryn L.; Yao, Song; Liu, Qian; Hu, Qiang; Haddad, Stephen A.; Sucheston-Campbell, Lara; Bensen, Jeannette T.; Bandera, Elisa V.; Rosenberg, Lynn; Liu, Song; Haiman, Christopher A.; Olshan, Andrew F.; Palmer, Julie R.; Ambrosone, Christine B.

2016-01-01

Leveraging population-distinct linkage equilibrium (LD) patterns, trans-ethnic follow-up of variants discovered from genome-wide association studies (GWAS) has proved to be useful in facilitating the identification of bona fide causal variants. We previously developed the preferential LD approach, a novel method that successfully identified causal variants driving the GWAS signals within European-descent populations even when the causal variants were only weakly linked with the GWAS-discovered variants. To evaluate the performance of our approach in a trans-ethnic setting, we applied it to follow up breast cancer GWAS hits identified mostly from populations of European ancestry in African Americans (AA). We evaluated 74 breast cancer GWAS variants in 8,315 AA women from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Only 27% of them were associated with breast cancer risk at significance level α=0.05, suggesting race-specificity of the identified breast cancer risk loci. We followed up on those replicated GWAS hits in the AMBER consortium utilizing the preferential LD approach, to search for causal variants or better breast cancer markers from the 1000 Genomes variant catalog. Our approach identified stronger breast cancer markers for 80% of the GWAS hits with at least nominal breast cancer association, and in 81% of these cases, the marker identified was among the top 10 of all 1000 Genomes variants in the corresponding locus. The results support trans-ethnic application of the preferential LD approach in search for candidate causal variants, and may have implications for future genetic research of breast cancer in AA women. PMID:27825120

Evaluating a Computational Model of Social Causality and Responsibility

DTIC Science & Technology

2006-01-01

Evaluating a Computational Model of Social Causality and Responsibility Wenji Mao University of Southern California Institute for Creative...empirically evaluate a computa- tional model of social causality and responsibility against human social judgments. Results from our experimental...developed a general computational model of social cau- sality and responsibility [10, 11] that formalizes the factors people use in reasoning about

A Systematic Review and Meta-Analysis of Risk Factors for Sexual Transmission of HIV in India

PubMed Central

Arora, Paul; Nagelkerke, Nico J. D.; Jha, Prabhat

2012-01-01

Background Approximately 2.4 million people are living with HIV in India. This large disease burden, and potential for epidemic spread in some areas, demands a full understanding of transmission in that country. We wished to quantify the effects of key sexual risk factors for HIV infection for each gender and among high- and low-HIV risk populations in India. Methodology We conducted a systematic review of sexual risk factors for HIV infection from 35 published studies. Risk factors analyzed were: male circumcision/religion, Herpes Simplex Virus 2, syphilis, gonorrhoea, genital ulcer, multiple sexual partners and commercial sex. Studies were included if they met predetermined criteria. Data were extracted and checked by two researchers and random-effects meta analysis of effects was conducted. Heterogeneity in effect estimates was examined by I2 statistic. Publication bias was tested by Begg's test and funnel plots. Meta regression was used to assess effect modification by various study attributes. Results All risk factors were significantly associated with HIV status. The factor most strongly associated with HIV for both sexes was HSV-2 infection (ORmen: 5.87; 95%CI: 2.46–14.03; ORwomen: 6.44; 95%CI: 3.22–12.86). The effect of multiple sexual partners was similar among men (OR = 2.46; 95%CI: 1.91–3.17,) and women (OR = 2.02; 95%CI: 1.43–2.87) and when further stratified by HIV-risk group. The association between HSV-2 and HIV prevalence was consistently stronger than other STIs or self-reported genital ulcer. If the strong associations between HSV-2 and HIV were interpreted causally, these results implied that approximately half of the HIV infections observed in our study population were attributable to HSV-2 infection. Conclusions The risk factors examined in our analysis should remain targets of HIV prevention programs. Our results confirm that sexual risk factors for HIV infection continue to be an important part of Indian HIV epidemic 26 years after it began. PMID:22937158

Public beliefs about causes and risk factors for mental disorders: a comparison of Japan and Australia

PubMed Central

Nakane, Yoshibumi; Jorm, Anthony F; Yoshioka, Kumiko; Christensen, Helen; Nakane, Hideyuki; Griffiths, Kathleen M

2005-01-01

Background Surveys of the public in a range of Western countries have shown a predominant belief in social stressors as causes of mental disorders. However, there has been little direct cross-cultural comparison. Here we report a comparison of public beliefs about the causes of mental disorders in Japan and Australia. Methods Surveys of the public were carried out in each country using as similar a methodology as feasible. In both countries, household interviews were carried out concerning beliefs about causes and risk factors in relation to one of four case vignettes, describing either depression, depression with suicidal thoughts, early schizophrenia or chronic schizophrenia. In Japan, the survey involved 2000 adults aged between 20 and 69 from 25 regional sites spread across the country. In Australia, the survey involved a national sample of 3998 adults aged 18 years or over. Results In both countries, both social and personal vulnerability causes were commonly endorsed across all vignettes. The major differences in causal beliefs were that Australians were more likely to believe in infection, allergy and genetics, while Japanese were more likely to endorse "nervous person" and "weakness of character". For risk factors, Australians tended to believe that women, the young and the poor were more at risk of depression, but these were not seen as higher risk groups by Japanese. Conclusion In both Japan and Australia, the public has a predominant belief in social causes and risk factors, with personal vulnerability factors also seen as important. However, there are also some major differences between the countries. The belief in weakness of character as a cause, which was stronger in Japan, is of particular concern because it may reduce the likelihood of seeking professional help and support from others. PMID:16174303

[Does the recent psychosocial research consider the perspective of developmental psychopathology?].

PubMed

Glaesmer, Heide; Petermann, Franz; Schüssler, Gerhard

2009-10-01

Developmental psychopathology is studying the development of psychological disorders with a life course perspective and an interdisciplinary approach considering the interplay of biological, psychological and social factors in complex models. The bibliometric analysis examines the implementation of this concept in the recent psychosocial research in the German-speaking area. Volumes 2007 and 2008 of three German psychological journals "Zeitschrift für Psychotherapie, Psychosomatik und Medizinische Psychologie", "Zeitschrift für Psychosomatische Medizin und Psychotherapie", and "Zeitschrift für Psychiatrie, Psychologie und Psychotherapie" were screened for articles dealing with issues of developmental psychopathology. 46 articles were identified and evaluated. Several aspects of developmental psychopathology are considered in a vast number of studies, but there is a main focus on risk factors, but not on protective factors and most of the studies are based on cross-sectional designs. Most of the recent practice in psychosocial research is not beneficial for the identification of causal effects or the complex interplay of risk and protective factors in the development of psychological disorders. Thus, longitudinal studies, taking biological, psychological and social factors and their interplay into account are essential to meet the requirement of developmental psychopathology. Georg Thieme Verlag KG Stuttgart. New York.

Understanding causes of fall and struck-by incidents: What differentiates construction safety in the Arabian Gulf region?

PubMed

Fass, Simon; Yousef, Rami; Liginlal, Divakaran; Vyas, Priyanka

2017-01-01

Rapid growth in the Arabian Gulf region has fueled an explosive pace of construction and a rise in risks of occupational injury. Scarcity of pertinent data, however, makes it hard to determine whether accident characteristics, causal factors and remedial interventions identified elsewhere apply to the Gulf in comparable ways. This difficulty stems from unusual construction sector characteristics, notably a heterogeneous mix of expatriate laborers and firms working without a common language, work culture or labor practices. Does this change the mix of accident types or the ranking of main causes and priority remedies? To answer this question, a sample of 519 incident records was analyzed to determine whether accident types and frequencies are comparable to elsewhere. Site safety experts were then interviewed to determine whether rankings of factors and interventions should be similar. Findings are that types are indeed comparable, but the rankings of factors and interventions may not be. Main factors have to do with worker skills and training, experience, use of safety gear and risk perception. The overarching safety issue, however, is that firms and governments do not have strong incentive to address these factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

University of North Carolina Caries Risk Assessment Study: comparisons of high risk prediction, any risk prediction, and any risk etiologic models.

PubMed

Beck, J D; Weintraub, J A; Disney, J A; Graves, R C; Stamm, J W; Kaste, L M; Bohannan, H M

1992-12-01

The purpose of this analysis is to compare three different statistical models for predicting children likely to be at risk of developing dental caries over a 3-yr period. Data are based on 4117 children who participated in the University of North Carolina Caries Risk Assessment Study, a longitudinal study conducted in the Aiken, South Carolina, and Portland, Maine areas. The three models differed with respect to either the types of variables included or the definition of disease outcome. The two "Prediction" models included both risk factor variables thought to cause dental caries and indicator variables that are associated with dental caries, but are not thought to be causal for the disease. The "Etiologic" model included only etiologic factors as variables. A dichotomous outcome measure--none or any 3-yr increment, was used in the "Any Risk Etiologic model" and the "Any Risk Prediction Model". Another outcome, based on a gradient measure of disease, was used in the "High Risk Prediction Model". The variables that are significant in these models vary across grades and sites, but are more consistent among the Etiologic model than the Predictor models. However, among the three sets of models, the Any Risk Prediction Models have the highest sensitivity and positive predictive values, whereas the High Risk Prediction Models have the highest specificity and negative predictive values. Considerations in determining model preference are discussed.

The risk perception paradox--implications for governance and communication of natural hazards.

PubMed

Wachinger, Gisela; Renn, Ortwin; Begg, Chloe; Kuhlicke, Christian

2013-06-01

This article reviews the main insights from selected literature on risk perception, particularly in connection with natural hazards. It includes numerous case studies on perception and social behavior dealing with floods, droughts, earthquakes, volcano eruptions, wild fires, and landslides. The review reveals that personal experience of a natural hazard and trust--or lack of trust--in authorities and experts have the most substantial impact on risk perception. Cultural and individual factors such as media coverage, age, gender, education, income, social status, and others do not play such an important role but act as mediators or amplifiers of the main causal connections between experience, trust, perception, and preparedness to take protective actions. When analyzing the factors of experience and trust on risk perception and on the likeliness of individuals to take preparedness action, the review found that a risk perception paradox exists in that it is assumed that high risk perception will lead to personal preparedness and, in the next step, to risk mitigation behavior. However, this is not necessarily true. In fact, the opposite can occur if individuals with high risk perception still choose not to personally prepare themselves in the face of a natural hazard. Therefore, based on the results of the review, this article offers three explanations suggesting why this paradox might occur. These findings have implications for future risk governance and communication as well as for the willingness of individuals to invest in risk preparedness or risk mitigation actions. © 2012 Society for Risk Analysis.

Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.

PubMed

van der Harst, Pim; Verweij, Niek

2018-02-02

Coronary artery disease (CAD) is a complex phenotype driven by genetic and environmental factors. Ninety-seven genetic risk loci have been identified to date, but the identification of additional susceptibility loci might be important to enhance our understanding of the genetic architecture of CAD. To expand the number of genome-wide significant loci, catalog functional insights, and enhance our understanding of the genetic architecture of CAD. We performed a genome-wide association study in 34 541 CAD cases and 261 984 controls of UK Biobank resource followed by replication in 88 192 cases and 162 544 controls from CARDIoGRAMplusC4D. We identified 75 loci that replicated and were genome-wide significant ( P <5×10 -8 ) in meta-analysis, 13 of which had not been reported previously. Next, to further identify novel loci, we identified all promising ( P <0.0001) loci in the CARDIoGRAMplusC4D data and performed reciprocal replication and meta-analyses with UK Biobank. This led to the identification of 21 additional novel loci reaching genome-wide significance ( P <5×10 -8 ) in meta-analysis. Finally, we performed a genome-wide meta-analysis of all available data revealing 30 additional novel loci ( P <5×10 -8 ) without further replication. The increase in sample size by UK Biobank raised the number of reconstituted gene sets from 4.2% to 13.9% of all gene sets to be involved in CAD. For the 64 novel loci, 155 candidate causal genes were prioritized, many without an obvious connection to CAD. Fine mapping of the 161 CAD loci generated lists of credible sets of single causal variants and genes for functional follow-up. Genetic risk variants of CAD were linked to development of atrial fibrillation, heart failure, and death. We identified 64 novel genetic risk loci for CAD and performed fine mapping of all 161 risk loci to obtain a credible set of causal variants. The large expansion of reconstituted gene sets argues in favor of an expanded omnigenic model view on the genetic architecture of CAD. © 2017 The Authors.

Expert explanations of honeybee losses in areas of extensive agriculture in France: Gaucho® compared with other supposed causal factors

NASA Astrophysics Data System (ADS)

Maxim, L.; van der Sluijs, J. P.

2010-01-01

Debates on causality are at the core of controversies as regards environmental changes. The present paper presents a new method for analyzing controversies on causality in a context of social debate and the results of its empirical testing. The case study used is the controversy as regards the role played by the insecticide Gaucho®, compared with other supposed causal factors, in the substantial honeybee (Apis mellifera L.) losses reported to have occurred in France between 1994 and 2004. The method makes use of expert elicitation of the perceived strength of evidence regarding each of Bradford Hill's causality criteria, as regards the link between each of eight possible causal factors identified in attempts to explain each of five signs observed in honeybee colonies. These judgments are elicited from stakeholders and experts involved in the debate, i.e., representatives of Bayer Cropscience, of the Ministry of Agriculture, of the French Food Safety Authority, of beekeepers and of public scientists. We show that the intense controversy observed in confused and passionate public discourses is much less salient when the various arguments are structured using causation criteria. The contradictions between the different expert views have a triple origin: (1) the lack of shared definition and quantification of the signs observed in colonies; (2) the lack of specialist knowledge on honeybees; and (3) the strategic discursive practices associated with the lack of trust between experts representing stakeholders having diverging stakes in the case.

Investigating the possible causal role of coffee consumption with prostate cancer risk and progression using Mendelian randomization analysis.

PubMed

Taylor, Amy E; Martin, Richard M; Geybels, Milan S; Stanford, Janet L; Shui, Irene; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay-Tee; Blot, William; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Donovan, Jenny; Munafò, Marcus R

2017-01-15

Coffee consumption has been shown in some studies to be associated with lower risk of prostate cancer. However, it is unclear if this association is causal or due to confounding or reverse causality. We conducted a Mendelian randomisation analysis to investigate the causal effects of coffee consumption on prostate cancer risk and progression. We used two genetic variants robustly associated with caffeine intake (rs4410790 and rs2472297) as proxies for coffee consumption in a sample of 46,687 men of European ancestry from 25 studies in the PRACTICAL consortium. Associations between genetic variants and prostate cancer case status, stage and grade were assessed by logistic regression and with all-cause and prostate cancer-specific mortality using Cox proportional hazards regression. There was no clear evidence that a genetic risk score combining rs4410790 and rs2472297 was associated with prostate cancer risk (OR per additional coffee increasing allele: 1.01, 95% CI: 0.98,1.03) or having high-grade compared to low-grade disease (OR: 1.01, 95% CI: 0.97,1.04). There was some evidence that the genetic risk score was associated with higher odds of having nonlocalised compared to localised stage disease (OR: 1.03, 95% CI: 1.01, 1.06). Amongst men with prostate cancer, there was no clear association between the genetic risk score and all-cause mortality (HR: 1.00, 95% CI: 0.97,1.04) or prostate cancer-specific mortality (HR: 1.03, 95% CI: 0.98,1.08). These results, which should have less bias from confounding than observational estimates, are not consistent with a substantial effect of coffee consumption on reducing prostate cancer incidence or progression. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Risk factors for persistent Aspergillus respiratory isolation in cystic fibrosis.

PubMed

Hong, Gina; Psoter, Kevin J; Jennings, Mark T; Merlo, Christian A; Boyle, Michael P; Hadjiliadis, Denis; Kawut, Steven M; Lechtzin, Noah

2018-02-12

Aspergillus species are increasingly detected in the respiratory tracts of individuals with cystic fibrosis (CF), and chronic Aspergillus fumigatus is associated with more frequent hospitalizations for pulmonary exacerbations. However, patient and clinical factors that may contribute to the acquisition of persistent Aspergillus infection have yet to be identified. The objective of this study was to identify risk factors for development of Aspergillus respiratory isolation in CF. A retrospective cohort study of participants in the CF Foundation Patient Registry between 2006 and 2012 was conducted. Generalized estimating equation models were used to evaluate the association between the development of persistent Aspergillus respiratory isolation and individual level demographic and clinical characteristics. Among 16,095 individuals with CF followed from 2006 to 2012, 1541 (9.6%) subjects developed persistent Aspergillus isolation. White race (Odds Ratio [OR] 1.74, 95% confidence interval 1.23, 2.48, p<0.001) and pancreatic insufficiency (OR 1.50, 95% CI 1.09, 2.06, p<0.001) were found to be risk factors for persistent Aspergillus isolation. Chronic therapies, including inhaled antibiotics (OR 1.33; 95% CI 1.21, 1.46), macrolides (OR 1.23, 95% CI 1.14, 1.32, p<0.001), and inhaled corticosteroids (OR 1.13, 95% CI 1.04, 1.20, p<0.001) were also independently associated with an increased risk for persistent Aspergillus isolation. We identified macrolides and inhaled antibiotics, which individually have been shown to improve CF outcomes, and inhaled corticosteroids as risk factors for developing persistent Aspergillus isolation. Further work is needed to determine whether these associations are causal or due to confounding by other factors. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Causal Relationships between the Psychological Acceptance Process of Athletic Injury and Athletic Rehabilitation Behavior

PubMed Central

Tatsumi, Tomonori; Takenouchi, Takashi

2014-01-01

[Purpose] The purpose of this study was to examine the causal relationships between the psychological acceptance process of athletic injury and athletic-rehabilitation behavior. [Subjects] One hundred forty-four athletes who had injury experiences participated in this study, and 133 (mean age = 20.21 years, SD = 1.07; mean weeks without playing sports = 7.97 weeks, SD = 11.26) of them provided valid questionnaire responses which were subjected to analysis. [Methods] The subjects were asked to answer our originally designed questionnaire, the Psychosocial Recovery Factor Scale (PSRF-S), and two other pre-existing scales, the Athletic Injury Psychological Acceptance Scale and the Athletic-Rehabilitation Dedication Scale. [Results] The results of factor analysis indicate “emotional stability”, “social competence in the team”, “temporal perspective”, and “communication with the teammates” are factors of the PSRF-S. Lastly, the causal model in which psychosocial recovery factors are mediated by psychological acceptance of athletic injury, and influence on rehabilitation behaviors, was examined using structural equation modeling (SEM). The results of SEM indicate that the factors of emotional stability and temporal perspective are mediated by the psychological acceptance of the injury, which positively influences athletic-rehabilitation dedication. [Conclusion] The causal model was confirmed to be valid. PMID:25202190

Two-step epigenetic Mendelian randomization: a strategy for establishing the causal role of epigenetic processes in pathways to disease

PubMed Central

Relton, Caroline L; Davey Smith, George

2012-01-01

The burgeoning interest in the field of epigenetics has precipitated the need to develop approaches to strengthen causal inference when considering the role of epigenetic mediators of environmental exposures on disease risk. Epigenetic markers, like any other molecular biomarker, are vulnerable to confounding and reverse causation. Here, we present a strategy, based on the well-established framework of Mendelian randomization, to interrogate the causal relationships between exposure, DNA methylation and outcome. The two-step approach first uses a genetic proxy for the exposure of interest to assess the causal relationship between exposure and methylation. A second step then utilizes a genetic proxy for DNA methylation to interrogate the causal relationship between DNA methylation and outcome. The rationale, origins, methodology, advantages and limitations of this novel strategy are presented. PMID:22422451

Actors, observers, and causal attributions of homelessness: Differences in attribution for the causes of homelessness among domiciled and homeless people in Madrid (Spain).

PubMed

Vázquez, José Juan; Panadero, Sonia; Zúñiga, Claudia

2017-01-01

The study analyzes the differences in causal attributions of homelessness and attributions of responsibility among the members of 3 groups: homeless group, consisting of a representative sample of homeless people in Madrid, Spain (n = 188); domiciled service-users group, consisting of people at risk of homelessness (n = 164); and domiciled nonservice-users group, consisting of people at no imminent risk of homelessness (n = 180). The domiciled service-users group and domiciled nonservice-users group were matched to the homeless group or sex, age, and nationality. The article also analyzes homeless people's causal attributions as regards their own situation. The results show that compared with the domiciled nonservice-users group, a higher percentage of members of the homeless group and domiciled service-users group attributed homelessness to individualistic causes and they blamed homeless people for their situation to a greater extent. The results also show that there was no "actor-observer bias" in causal attributions for homelessness in Madrid. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Civil war: is it all about disease and xenophobia? A comment on Letendre, Fincher & Thornhill.

PubMed

Hendrix, Cullen S; Gleditsch, Kristian Skrede

2012-02-01

Letendre, Fincher & Thornhill (2010) argue that pathogen intensity provides the ultimate explanation for why some countries are more prone to civil war than others. They argue that the economic and political factors highlighted in previous research on civil war are largely caused by underlying differences in pathogen intensity, and contend that disease proneness increases the risk of civil war through its effects on resource competition and xenophobia. They present empirical evidence that they interpret as consistent with their argument: a statistically significant correlation between pathogen intensity and civil war onset. In this comment, we raise concerns over their interpretation of the empirical evidence and their proposed causal mechanisms. We find that the data provide stronger evidence for the reverse causal relationship, namely that civil war causes disease to become more prevalent. This finding is consistent with the literatures on the public health effects of civil war as well as research on state capacity and public health. © 2011 The Authors. Biological Reviews © 2011 Cambridge Philosophical Society.

The conundrum of causality in tumor virology: the cases of KSHV and MCV.

PubMed

Moore, Patrick S; Chang, Yuan

2014-06-01

Controversy has plagued tumor virology since the first tumor viruses were described over 100 years ago. Methods to establish cancer causation, such as Koch's postulates, work poorly or not at all for these viruses. Kaposi's sarcoma herpesvirus (KSHV/HHV8) and Merkel cell polyomavirus (MCV) were both found using nucleic acid identification methods but they represent opposite poles in the patterns for tumor virus epidemiology. KSHV is uncommon and has specific risk factors that contribute to infection and subsequent cancers. MCV and Merkel cell carcinoma (MCC), in contrast, is an example in which mutations to our normal viral flora contribute to cancer. Given the near-ubiquity of human MCV infection, establishing cancer causality relies on molecular evidence that does not fit comfortably within traditional infectious disease epidemiological models. These two viruses reveal some of the challenges and opportunities for inferring viral cancer causation in the age of molecular biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exploring Individual Differences in Online Addictions: the Role of Identity and Attachment.

PubMed

Monacis, Lucia; de Palo, Valeria; Griffiths, Mark D; Sinatra, Maria

2017-01-01

Research examining the development of online addictions has grown greatly over the last decade with many studies suggesting both risk factors and protective factors. In an attempt to integrate the theories of attachment and identity formation, the present study investigated the extent to which identity styles and attachment orientations account for three types of online addiction (i.e., internet addiction, online gaming addiction, and social media addiction). The sample comprised 712 Italian students (381 males and 331 females) recruited from schools and universities who completed an offline self-report questionnaire. The findings showed that addictions to the internet, online gaming, and social media were interrelated and were predicted by common underlying risk and protective factors. Among identity styles, 'informational' and 'diffuse-avoidant' styles were risk factors, whereas 'normative' style was a protective factor. Among attachment dimensions, the 'secure' attachment orientation negatively predicted the three online addictions, and a different pattern of causal relationships were observed between the styles underlying 'anxious' and 'avoidant' attachment orientations. Hierarchical multiple regressions demonstrated that identity styles explained between 21.2 and 30% of the variance in online addictions, whereas attachment styles incrementally explained between 9.2 and 14% of the variance in the scores on the three addiction scales. These findings highlight the important role played by identity formation in the development of online addictions.

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.

PubMed

Wray, Naomi R; Ripke, Stephan; Mattheisen, Manuel; Trzaskowski, Maciej; Byrne, Enda M; Abdellaoui, Abdel; Adams, Mark J; Agerbo, Esben; Air, Tracy M; Andlauer, Till M F; Bacanu, Silviu-Alin; Bækvad-Hansen, Marie; Beekman, Aartjan F T; Bigdeli, Tim B; Binder, Elisabeth B; Blackwood, Douglas R H; Bryois, Julien; Buttenschøn, Henriette N; Bybjerg-Grauholm, Jonas; Cai, Na; Castelao, Enrique; Christensen, Jane Hvarregaard; Clarke, Toni-Kim; Coleman, Jonathan I R; Colodro-Conde, Lucía; Couvy-Duchesne, Baptiste; Craddock, Nick; Crawford, Gregory E; Crowley, Cheynna A; Dashti, Hassan S; Davies, Gail; Deary, Ian J; Degenhardt, Franziska; Derks, Eske M; Direk, Nese; Dolan, Conor V; Dunn, Erin C; Eley, Thalia C; Eriksson, Nicholas; Escott-Price, Valentina; Kiadeh, Farnush Hassan Farhadi; Finucane, Hilary K; Forstner, Andreas J; Frank, Josef; Gaspar, Héléna A; Gill, Michael; Giusti-Rodríguez, Paola; Goes, Fernando S; Gordon, Scott D; Grove, Jakob; Hall, Lynsey S; Hannon, Eilis; Hansen, Christine Søholm; Hansen, Thomas F; Herms, Stefan; Hickie, Ian B; Hoffmann, Per; Homuth, Georg; Horn, Carsten; Hottenga, Jouke-Jan; Hougaard, David M; Hu, Ming; Hyde, Craig L; Ising, Marcus; Jansen, Rick; Jin, Fulai; Jorgenson, Eric; Knowles, James A; Kohane, Isaac S; Kraft, Julia; Kretzschmar, Warren W; Krogh, Jesper; Kutalik, Zoltán; Lane, Jacqueline M; Li, Yihan; Li, Yun; Lind, Penelope A; Liu, Xiaoxiao; Lu, Leina; MacIntyre, Donald J; MacKinnon, Dean F; Maier, Robert M; Maier, Wolfgang; Marchini, Jonathan; Mbarek, Hamdi; McGrath, Patrick; McGuffin, Peter; Medland, Sarah E; Mehta, Divya; Middeldorp, Christel M; Mihailov, Evelin; Milaneschi, Yuri; Milani, Lili; Mill, Jonathan; Mondimore, Francis M; Montgomery, Grant W; Mostafavi, Sara; Mullins, Niamh; Nauck, Matthias; Ng, Bernard; Nivard, Michel G; Nyholt, Dale R; O'Reilly, Paul F; Oskarsson, Hogni; Owen, Michael J; Painter, Jodie N; Pedersen, Carsten Bøcker; Pedersen, Marianne Giørtz; Peterson, Roseann E; Pettersson, Erik; Peyrot, Wouter J; Pistis, Giorgio; Posthuma, Danielle; Purcell, Shaun M; Quiroz, Jorge A; Qvist, Per; Rice, John P; Riley, Brien P; Rivera, Margarita; Saeed Mirza, Saira; Saxena, Richa; Schoevers, Robert; Schulte, Eva C; Shen, Ling; Shi, Jianxin; Shyn, Stanley I; Sigurdsson, Engilbert; Sinnamon, Grant B C; Smit, Johannes H; Smith, Daniel J; Stefansson, Hreinn; Steinberg, Stacy; Stockmeier, Craig A; Streit, Fabian; Strohmaier, Jana; Tansey, Katherine E; Teismann, Henning; Teumer, Alexander; Thompson, Wesley; Thomson, Pippa A; Thorgeirsson, Thorgeir E; Tian, Chao; Traylor, Matthew; Treutlein, Jens; Trubetskoy, Vassily; Uitterlinden, André G; Umbricht, Daniel; Van der Auwera, Sandra; van Hemert, Albert M; Viktorin, Alexander; Visscher, Peter M; Wang, Yunpeng; Webb, Bradley T; Weinsheimer, Shantel Marie; Wellmann, Jürgen; Willemsen, Gonneke; Witt, Stephanie H; Wu, Yang; Xi, Hualin S; Yang, Jian; Zhang, Futao; Arolt, Volker; Baune, Bernhard T; Berger, Klaus; Boomsma, Dorret I; Cichon, Sven; Dannlowski, Udo; de Geus, E C J; DePaulo, J Raymond; Domenici, Enrico; Domschke, Katharina; Esko, Tõnu; Grabe, Hans J; Hamilton, Steven P; Hayward, Caroline; Heath, Andrew C; Hinds, David A; Kendler, Kenneth S; Kloiber, Stefan; Lewis, Glyn; Li, Qingqin S; Lucae, Susanne; Madden, Pamela F A; Magnusson, Patrik K; Martin, Nicholas G; McIntosh, Andrew M; Metspalu, Andres; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Nordentoft, Merete; Nöthen, Markus M; O'Donovan, Michael C; Paciga, Sara A; Pedersen, Nancy L; Penninx, Brenda W J H; Perlis, Roy H; Porteous, David J; Potash, James B; Preisig, Martin; Rietschel, Marcella; Schaefer, Catherine; Schulze, Thomas G; Smoller, Jordan W; Stefansson, Kari; Tiemeier, Henning; Uher, Rudolf; Völzke, Henry; Weissman, Myrna M; Werge, Thomas; Winslow, Ashley R; Lewis, Cathryn M; Levinson, Douglas F; Breen, Gerome; Børglum, Anders D; Sullivan, Patrick F

2018-05-01

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

Disease ecology and the global emergence of zoonotic pathogens.

PubMed

Wilcox, Bruce A; Gubler, Duane J

2005-09-01

The incidence and frequency of epidemic transmission of zoonotic diseases, both known and newly recognized, has increased dramatically in the past 30 years. It is thought that this dramatic disease emergence is primarily the result of the social, demographic, and environmental transformation that has occurred globally since World War II. However, the causal linkages have not been elucidated. Investigating emerging zoonotic pathogens as an ecological phenomenon can provide significant insights as to why some of these pathogens have jumped species and caused major epidemics in humans. A review of concepts and theory from biological ecology and of causal factors in disease emergence previously described suggests a general model of global zoonotic disease emergence. The model links demographic and societal factors to land use and land cover change whose associated ecological factors help explain disease emergence. The scale and magnitude of these changes are more significant than those associated with climate change, the effects of which are largely not yet understood. Unfortunately, the complex character and non-linear behavior of the human-natural systems in which host-pathogen systems are embedded makes specific incidences of disease emergence or epidemics inherently difficult to predict. Employing a complex systems analytical approach, however, may show how a few key ecological variables and system properties, including the adaptive capacity of institutions, explains the emergence of infectious diseases and how an integrated, multi-level approach to zoonotic disease control can reduce risk.

Does being drunk or high cause HIV sexual risk behavior? A systematic review of drug administration studies.

PubMed

Berry, Meredith S; Johnson, Matthew W

2018-01-01

HIV sexual risk behavior is broadly associated with substance use. Yet critical questions remain regarding the potential causal link between substance use (e.g., intoxication) and HIV sexual risk behavior. The present systematic review was designed to examine and synthesize the existing literature regarding the effects of substance administration on HIV sexual risk behavior. Randomized controlled experiments investigating substance administration and HIV sexual risk behavior (e.g., likelihood of condom use in a casual sex scenario) were included. Across five databases, 2750 titles/abstracts were examined and forty-three total peer reviewed published manuscripts qualified (few were multi-study manuscripts, and those details are outlined in the text). The majority of articles investigated the causal role of acute alcohol administration on HIV sexual risk behavior, although one article investigated the effects of acute THC administration, one the effects of acute cocaine administration, and two the effects of buspirone. The results of this review suggest a causal role in acute alcohol intoxication increasing HIV sexual risk decision-making. Although evidence is limited with other substances, cocaine administration also appears to increase sexual risk, while acute cannabis and buspirone maintenance may decrease sexual risk. In the case of alcohol intoxication, the pharmacological effects independently contribute to HIV sexual risk decision-making, and these effects are exacerbated by alcohol expectancies, increased arousal, and delay to condom availability. Comparisons across studies showed that cocaine led to greater self-reported sexual arousal than alcohol, potentially suggesting a different risk profile. HIV prevention measures should take these substance administration effects into account. Increasing the amount of freely and easily accessible condoms to the public may attenuate the influence of acute intoxication on HIV sexual risk decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

An ecological analysis of prison overcrowding and suicide rates in England and Wales, 2000-2014.

PubMed

van Ginneken, Esther F J C; Sutherland, Alex; Molleman, Toon

Prisoners are at a greatly increased risk of suicides compared to the general population. Differences in suicide risk can be partly explained by individual risk factors, but the contribution of prison characteristics remains unclear. Overcrowded prisons have higher suicide rates, but this may be related to prison function, security level, population size and turnover. The aim of the current study was to investigate the contribution of each of these prison characteristics to suicide rates, using data from the Ministry of Justice for adult prisons in England and Wales from 2000 to 2014. Negative binomial regression analysis showed that larger population size, higher turnover, higher security and public management were associated with higher suicide rates. When controlling for these factors, overcrowding was not found to be related to suicide rates. Questions remain about the causal mechanisms underlying variation in prison suicides and the impact of the lived experience of overcrowding. Further research is needed to examine the relative contribution of prison and prisoner characteristics to suicides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Age and Cancer Risk

PubMed Central

White, Mary C.; Holman, Dawn M.; Boehm, Jennifer E.; Peipins, Lucy A.; Grossman, Melissa; Henley, S. Jane

2015-01-01

This article challenges the idea that cancer cannot be prevented among older adults by examining different aspects of the relationship between age and cancer. Although the sequential patterns of aging cannot be changed, several age-related factors that contribute to disease risk can be. For most adults, age is coincidentally associated with preventable chronic conditions, avoidable exposures, and modifiable risk behaviors that are causally associated with cancer. Midlife is a period of life when the prevalence of multiple cancer risk factors is high and incidence rates begin to increase for many types of cancer. However, current evidence suggests that for most adults, cancer does not have to be an inevitable consequence of growing older. Interventions that support healthy environments, help people manage chronic conditions, and promote healthy behaviors may help people make a healthier transition from midlife to older age and reduce the likelihood of developing cancer. Because the number of adults reaching older ages is increasing rapidly, the number of new cancer cases will also increase if current incidence rates remain unchanged. Thus, the need to translate the available research into practice to promote cancer prevention, especially for adults at midlife, has never been greater. PMID:24512933

The Interaction Between Thyroid and Kidney Disease: An Overview of the Evidence

PubMed Central

Rhee, Connie M.

2016-01-01

Purpose of Review Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients, including those receiving dialysis. This review examines potential mechanistic links between thyroid and kidney disease; current evidence for hypothyroidism as a risk factor for de novo CKD and CKD progression; and studies of thyroid functional disorders, cardiovascular disease, and death in the CKD population. Recent Findings Epidemiologic data have demonstrated an incrementally higher prevalence of hypothyroidism with increasing severity of kidney dysfunction. Various thyroid functional test abnormalities are also commonly observed in CKD, due to alterations in thyroid hormone synthesis, metabolism, and regulation. While the mechanistic link between thyroid and kidney disease remains unclear, observational studies suggest hypothyroidism is associated with abnormal kidney structure and function. Previously thought to be a physiologic adaptation, recent studies show that hypothyroidism is associated with higher risk of cardiovascular disease and death in CKD. Summary A growing body of evidence suggests that hypothyroidism is a risk factor for incident CKD, CKD progression, and higher death risk in kidney disease patients. Rigorous studies are needed to determine impact of thyroid hormone replacement upon kidney disease progression, cardiovascular disease, and mortality, which may shed light into the causal implications of hypothyroidism in CKD. PMID:27428519

Helicobacter pylori infection and dementia: can actual data reinforce the hypothesis of a causal association?

PubMed

Adriani, A; Fagoonee, S; De Angelis, C; Altruda, F; Pellicano, R

2014-09-01

Helicobacter pylori (H. pylori) is involved in the development of several gastroduodenal diseases. Since the latest decade, several studies have reported on the link between chronic H. pylori infection and a variety of extragastric manifestations, including dementia. To identify the publications on the association between H. pylori and dementia, a MEDLINE search was conducted. Although case-control studies reported controversial data, a recent longitudinal population-based cohort study found that after 20 years of follow-up, 28.9% of H. pylori-positive versus 21.1% of H. pylori-negative subjects developed dementia. After correction for confounding factors, the infection was significantly associated with higher risk of developing dementia (P=0.04). Moreover, in another study evaluating the effect of H. pylori eradication on the progression of dementia in Alzheimer's disease patients with peptic ulcer, the cure of the bacterium was associated with a decreased risk of dementia progression compared to persistent infection. To date, defining H. pylori as a target for prevention or treatment of dementia remains a topic with much controversy but of essence, as any relationship would reduce, due to the cost-effectiveness of the therapy, a burden on the National Health Care budget. The need for extensive studies with appropriate epidemiological and clinical approaches is crucial to investigate a potential causal relationship.

A new quantitative approach to measure perceived work-related stress in Italian employees.

PubMed

Cevenini, Gabriele; Fratini, Ilaria; Gambassi, Roberto

2012-09-01

We propose a method for a reliable quantitative measure of subjectively perceived occupational stress applicable in any company to enhance occupational safety and psychosocial health, to enable precise prevention policies and intervention and to improve work quality and efficiency. A suitable questionnaire was telephonically administered to a stratified sample of the whole Italian population of employees. Combined multivariate statistical methods, including principal component, cluster and discriminant analyses, were used to identify risk factors and to design a causal model for understanding work-related stress. The model explained the causal links of stress through employee perception of imbalance between job demands and resources for responding appropriately, by supplying a reliable U-shaped nonlinear stress index, expressed in terms of values of human systolic arterial pressure. Low, intermediate and high values indicated demotivation (or inefficiency), well-being and distress, respectively. Costs for stress-dependent productivity shortcomings were estimated to about 3.7% of national income from employment. The method identified useful structured information able to supply a simple and precise interpretation of employees' well-being and stress risk. Results could be compared with estimated national benchmarks to enable targeted intervention strategies to protect the health and safety of workers, and to reduce unproductive costs for firms.

Impact of Childhood Malnutrition on Host Defense and Infection.

PubMed

Ibrahim, Marwa K; Zambruni, Mara; Melby, Christopher L; Melby, Peter C

2017-10-01

The global impact of childhood malnutrition is staggering. The synergism between malnutrition and infection contributes substantially to childhood morbidity and mortality. Anthropometric indicators of malnutrition are associated with the increased risk and severity of infections caused by many pathogens, including viruses, bacteria, protozoa, and helminths. Since childhood malnutrition commonly involves the inadequate intake of protein and calories, with superimposed micronutrient deficiencies, the causal factors involved in impaired host defense are usually not defined. This review focuses on literature related to impaired host defense and the risk of infection in primary childhood malnutrition. Particular attention is given to longitudinal and prospective cohort human studies and studies of experimental animal models that address causal, mechanistic relationships between malnutrition and host defense. Protein and micronutrient deficiencies impact the hematopoietic and lymphoid organs and compromise both innate and adaptive immune functions. Malnutrition-related changes in intestinal microbiota contribute to growth faltering and dysregulated inflammation and immune function. Although substantial progress has been made in understanding the malnutrition-infection synergism, critical gaps in our understanding remain. We highlight the need for mechanistic studies that can lead to targeted interventions to improve host defense and reduce the morbidity and mortality of infectious diseases in this vulnerable population. Copyright © 2017 American Society for Microbiology.

The Relative Predictive Contribution and Causal Role of Phoneme Awareness, Rhyme Awareness, and Verbal Short-Term Memory in Reading Skills: A Review

ERIC Educational Resources Information Center

Melby-Lervag, Monica

2012-01-01

The acknowledgement that educational achievement is highly dependent on successful reading development has led to extensive research on its underlying factors. A strong argument has been made for a causal relationship between reading and phoneme awareness; similarly, causal relations have been suggested for reading with short-term memory and rhyme…

The effects of stress-tension on depression and anxiety symptoms: evidence from a novel twin modelling analysis.

PubMed

Davey, C G; López-Solà, C; Bui, M; Hopper, J L; Pantelis, C; Fontenelle, L F; Harrison, B J

2016-11-01

Negative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs. A total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress-tension. We applied a recently developed twin regression methodology - Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) - to test for evidence consistent with the existence of 'causal' influences between the DASS factors. There was evidence consistent with the stress-tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001). Our findings suggest a critical role for stress-tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms.

Marijuana use and depression among adults: Testing for causal associations.

PubMed

Harder, Valerie S; Morral, Andrew R; Arkes, Jeremy

2006-10-01

To determine whether marijuana use predicts later development of depression after accounting for differences between users and non-users of marijuana. An ongoing longitudinal survey of 12 686 men and women beginning in 1979. The National Longitudinal Survey of Youth of 1979, a nationally representative sample from the United States. A total of 8759 adults (age range 29-37 years) interviewed in 1994 had complete data on past-year marijuana use and current depression. Self-reported past-year marijuana use was tested as an independent predictor of later adult depression using the Center for Epidemiologic Studies-Depression questionnaire. Individual's propensity to use marijuana was calculated using over 50 baseline covariates. Before adjusting for group differences, the odds of current depression among past-year marijuana users is 1.4 times higher (95% CI: 1.1, 1.9) than the odds of depression among the non-using comparison group. After adjustment, the odds of current depression among past-year marijuana users is only 1.1 times higher than the comparison group (95% CI: 0.8, 1.7). Similarly, adjustment eliminates significant associations between marijuana use and depression in four additional analyses: heavy marijuana use as the risk factor, stratifying by either gender or age, and using a 4-year lag-time between marijuana use and depression. After adjusting for differences in baseline risk factors of marijuana use and depression, past-year marijuana use does not significantly predict later development of depression. These findings are discussed in terms of their relevance for understanding possible causal effects of marijuana use on depression.

Urinary saturation: casual or causal risk factor in urolithiasis?

PubMed

Rodgers, Allen L

2014-07-01

To assess (i) the extent to which urinary supersaturation (SS) has successfully discriminated between stone formers and healthy individuals (N), (ii) whether absolute SS has diagnostic worth and (iii) whether high SS is the fundamental cause of stone formation per se. Google Scholar was used to identify studies in which urinary compositional data had been determined. In those cases where SS values were not given, or where other risk indices had been reported, they were (re-)calculated. Collected data were termed 'global' but were then 'filtered' according to stone type and protocols used for SS calculations. SS distribution plots for calcium oxalate, brushite and uric acid were constructed. Data were statistically analysed using the unpaired t-test and Mann-Whitney test. In all, 47 studies yielded 123 SS values for healthy individuals and 122 values for stone formers. The mean and median SS values were significantly greater in stone formers compared with healthy individuals in all but one of the comparisons. Wide variations in SS occurred for healthy individuals and stone formers. The two groups could not be separated. Absolute SS has no diagnostic worth. It is impossible to quantify the meaning of a 'high' SS value. Urines cannot be identified as originating from healthy individuals or stone formers based on their SS. SS should be determined in clinical and research settings for relative comparisons during the assessment of treatment efficacies. This study provides a compelling argument for SS being a casual factor rather than a causal one. © 2013 The Author. BJU International © 2013 BJU International.

Associations of Sleep Quality and Awake Physical Activity with Fluctuations in Nocturnal Blood Pressure in Patients with Cardiovascular Risk Factors

PubMed Central

Kadoya, Manabu; Koyama, Hidenori; Kurajoh, Masafumi; Naka, Mariko; Miyoshi, Akio; Kanzaki, Akinori; Kakutani, Miki; Shoji, Takuhito; Moriwaki, Yuji; Yamamoto, Tetsuya; Inaba, Masaaki; Namba, Mitsuyoshi

2016-01-01

Background Sleep quality and awake physical activity are important behavioral factors involved in the occurrence of cardiovascular diseases, potentially through nocturnal blood pressure (BP) changes. However, the impacts of quantitatively measured sleep quality and awake physical activity on BP fluctuation, and their relationships with several candidate causal factors for nocturnal hypertension are not well elucidated. Methods This cross-sectional study included 303 patients registered in the HSCAA study. Measurements included quantitatively determined sleep quality parameters and awake physical activity obtained by actigraph, nocturnal systolic BP (SBP) fall [100 × (1- sleep SBP/awake SBP ratio)], apnea hypopnea index, urinary sodium and cortisol secretion, plasma aldosterone concentration and renin activity, insulin resistance index, parameters of heart rate variability (HRV), and plasma brain-derived neurotrophic factor (BDNF). Results Simple regression analysis showed that time awake after sleep onset (r = -0.150), a parameter of sleep quality, and awake physical activity (r = 0.164) were significantly correlated with nocturnal SBP fall. Among those, time awake after sleep onset (β = -0.179) and awake physical activity (β = 0.190) were significantly and independently associated with nocturnal SBP fall in multiple regression analysis. In a subgroup of patients without taking anti-hypertensive medications, both time awake after sleep onset (β = -0.336) and awake physical activity (β = 0.489) were more strongly and independently associated with nocturnal SBP falls. Conclusion Sleep quality and awake physical activity were found to be significantly associated with nocturnal SBP fall, and that relationship was not necessarily confounded by candidate causal factors for nocturnal hypertension. PMID:27166822

Female babies and risk-aversion: Causal evidence from hospital wards.

PubMed

Pogrebna, Ganna; Oswald, Andrew J; Haig, David

2018-03-01

Using ultrasound scan data from paediatric hospitals, and the exogenous 'shock' of learning the gender of an unborn baby, the paper documents the first causal evidence that offspring gender affects adult risk-aversion. On a standard Holt-Laury criterion, parents of daughters, whether unborn or recently born, become almost twice as risk-averse as parents of sons. The study demonstrates this in longitudinal and cross-sectional data, for fathers and mothers, for babies in the womb and new-born children, and in a West European nation and East European nation. These findings may eventually aid our understanding of risky health behaviors and gender inequalities. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Infant acetylcholine, dopamine, and melatonin dysregulation: Neonatal biomarkers and causal factors for ASD and ADHD phenotypes.

PubMed

Hellmer, Kahl; Nyström, Pär

2017-03-01

Autism spectrum disorders (ASD) and ADHD are common neurodevelopmental disorders that benefit from early intervention but currently suffer from late detection and diagnosis: neurochemical dysregulations are extant already at birth but clinical phenotypes are not distinguishable until preschool age or later. The vast heterogeneity between subjects' phenotypes relates to interaction between multiple unknown factors, making research on factor causality insurmountable. To unlock this situation we pose the hypothesis that atypical pupillary light responses from rods, cones, and the recently discovered ipRGC system reflect early acetylcholine, melatonin, and dopamine dysregulation that are sufficient but not necessary factors for developing ASD and/or ADHD disorders. Current technology allows non-invasive cost-efficient assessment already from the first postnatal month. The benefits of the current proposal are: identification of clinical subgroups based on cause rather than phenotypes; facilitation of research on other causal factors; neonatal prediction of later diagnoses; and guidance for targeted therapeutical intervention. Copyright © 2017 Elsevier Ltd. All rights reserved.