Causal Determinants Research Articles

Warheads of Energy: Exploring the linkages between civilian nuclear power and nuclear weapons in seven countries

This paper focuses on the causal determinants of the accumulation of nuclear weapons, also known as vertical nuclear proliferation, in China, France, India, Pakistan, Russia, UK, and the US. It empirically analyzes the causal relationships between the civilian uses of nuclear energy, military expenditures, trade openness, and the stockpiling of nuclear warheads. Results from the Toda and Yamamoto (1995) version of the Granger non-causality test suggest a causal relationship in five of the seven states. A potential nuclear power lock-in into their energy systems induced by vertical proliferation aspirations is also plausible for some of the states. We suggest that military nuclear relationships affect energy system developments and impede a nuclear phase-out in the seven states. Emphasizing the mutually beneficial relationship between a state’s nuclear warhead stockpiles and its civil nuclear capabilities helps to explain nuclear incumbency and the future use of nuclear power in nuclear armed states. We also discuss the implications from our results for sociotechnical transition theories which usually neglect the role of military nuclear related factors in describing energy system trajectories.

Exploring the neurological exposome for precision prevention of neurodegenerative diseases – the role of diet

BACKGROUND AND AIM: The exposome represents the totality of exposures from conception onwards. Unravelling it requires to simultaneously identify, characterize and quantify exogenous and endogenous exposures and modifiable risk factors that predispose to and predict disease throughout the human life span. METHODS: Exposome science will help us understand the intricate web of relationships between environmental exposures, lifestyle, genetics and disease, contributing significantly to the determination of causal associations between environmental factors and human health. Determination of causality would support targeted interventions towards precision prevention, contributing significantly towards healthy aging. RESULTS:Aging brings a lot of physiological changes, usually accompanied by deterioration in cognitive function as a result of neurological degeneration, mediated by oxidative stress and inflammatory processes. However, this process does not follow a standardized course for all individuals, as a result of multiple factors. These factors include genetic susceptibility, exposure to environmental chemicals, lifestyle aspects such as poor nutrition, excessive alcohol ingestion, lack of exercise and stress, health status (e.g. hypertension or diabetes), as well as exposure to chemicals. Although diet is considered as a major exogenous factor, up-regulation of the inflammatory metabolic pathway and in many cases the oxidative stress pathway is triggered or amplified by other exogenous exposures such as exposure to man-made chemicals. Thus, exploring the role of diet in triggering and accelerating the progression of Alzheimer’s disease, should account for both the beneficial nutrients and the neurotoxicants associated with specific food items. High dimension biology tools based on a combination of omics technologies are able to identify the molecular fingerprints and pathway changes associated with specific dietary patterns, exposure to chemicals inducing oxidative stress (ambient air PM) and neuroinflammation (Hg) and genetic factors (ApoE e4 carriers). CONCLUSIONS:Exposomic analysis of the effect of diet on AD is expected to facilitate the coining and implementation of precision prevention strategies. KEYWORDS: Neurodegenerative outcomes, Exposome, Food/nutrition, Metabolomics

Revisiting the bipolar disorder with migraine phenotype: Clinical features and comorbidity

IntroductionTo evaluate the prevalence and clinical correlates of lifetime migraine among patients with bipolar disorder (BD). MethodsIn a cross-sectional study, we evaluated 721 adults with BD from the Mayo Clinic Bipolar Disorder Biobank and compared clinical correlates of those with and without a lifetime history of migraine. A structured clinical interview (DSM-IV) and a clinician-assessed questionnaire were utilized to establish a BD diagnosis, lifetime history of migraine, and clinical correlates. ResultsTwo hundred and seven (29%) BD patients had a lifetime history of migraine. BD patients with migraine were younger and more likely to be female as compared to those without migraine (p values <0.01). In a multivariate logistic regression model, younger age (OR=0.98, p<0.01), female sex (OR=2.02, p<0.01), higher shape/weight concern (OR=1.04, p=0.02), greater anxiety disorder comorbidities (OR=1.24, p<0.01), and evening chronotype (OR=1.65, p=0.03) were associated with migraine. In separate regression models for each general medical comorbidity (controlled for age, sex, and site), migraines were significantly associated with fibromyalgia (OR=3.17, p<0.01), psoriasis (OR=2.65, p=0.03), and asthma (OR=2.0, p<0.01). Participants with migraine were receiving ADHD medication (OR=1.53, p=0.05) or compounds associated with weight loss (OR=1.53, p=0.02) at higher rates compared to those without migraine. LimitationsStudy design precludes determination of causality. Migraine subtypes and features were not assessed. ConclusionsMigraine prevalence is high in BD and is associated with a more severe clinical burden that includes increased comorbidity with pain and inflammatory conditions. Further study of the BD-migraine phenotype may provide insight into common underlying neurobiological mechanisms.

Not so far east? The impact of Central-Eastern European imports on the Brexit referendum

ABSTRACT We explore the effect of the UK’s economic links with Central-Eastern Europe and China in the case of the Brexit referendum. First, we replicate and independently verify the Colantone and Stanig findings (2018a) on the effect of globalization on Brexit. Then, we extend their original analysis and demonstrate that although both Chinese and Central-Eastern European imports were significant causal determinants of the referendum’s outcome, exposure to Central-Eastern European imports was up to three times more important than exposure to Chinese imports. This may be due to cultural correlates of trade. Our analysis reveals that differences in media coverage between Central-Eastern European and Chinese economic news, as well as migrant population shares from these two regions, might have played a decisive role. Overall, the article also suggests that the import-shock method, as currently applied in the literature, is ill-suited to compare shocks with diverse origins.

Controversy and Debate : Questionable utility of the relative risk in clinical research: Paper 4 :Odds Ratios are far from “portable” — A call to use realistic models for effect variation in meta-analysis

ObjectiveRecently Doi et al. argued that risk ratios should be replaced with odds ratios in clinical research. We disagreed, and empirically documented the lack of portability of odds ratios, while Doi et al. defended their position. In this response we highlight important errors in their position. Study design and settingWe counter Doi et al.’s arguments by further examining the correlations of odds ratios, and risk ratios, with baseline risks in 20,198 meta-analyses from the Cochrane Database of Systematic Reviews. ResultsDoi et al.’s claim that odds ratios are portable is invalid because 1) their reasoning is circular: they assume a model under which the odds ratio is constant and show that under such a model the odds ratio is portable; 2) the method they advocate to convert odds ratios to risk ratios is biased; 3) their empirical example is readily-refuted by counter-examples of meta-analyses in which the risk ratio is portable but the odds ratio isn't; and 4) they fail to consider the causal determinants of meta-analytic inclusion criteria: Doi et al. mistakenly claim that variation in odds ratios with different baseline risks in meta-analyses is due to collider bias. Empirical comparison between the correlations of odds ratios, and risk ratios, with baseline risks show that the portability of odds ratios and risk ratios varies across settings. ConclusionThe suggestion to replace risk ratios with odds ratios is based on circular reasoning and a confusion of mathematical and empirical results. It is especially misleading for meta-analyses and clinical guidance. Neither the odds ratio nor the risk ratio is universally portable. To address this lack of portability, we reinforce our suggestion to report variation in effect measures conditioning on modifying factors such as baseline risk; understanding such variation is essential to patient-centered practice.

Severe Acute Respiratory Syndrome Coronavirus 2 Reinfection Cases Corroborated by Sequencing.

ABSTRACT.Evaluating cases of reinfection may offer some insight into areas for further investigation regarding durability of immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sixty cases of reinfection with viral sequencing were identified in PubMed, Embase, Web of Science, and medRxiv before May 1, 2021.Episodes of infection were separated by a median of 116 days. Severity of illness was greater among individuals reinfected within 90 days of initial infection, no asymptomatic initial cases developed severe reinfection, nearly half of cases had suspected escape variants, and nearly all individuals tested following reinfection were found to have detectable levels of anti-SARS-CoV-2 antibodies. This analysis is limited by the heterogeneous methods used among reports. Reinfection continues to be relatively rare. As the case rate presumably increases over time, this review will inform measurements to determine the natural history and causal determinants of reinfection in more rigorous observational cohort studies and other standardized surveillance approaches.

Causal Modelling in Fertility Research: A Review of the Literature and an Application to a Parental Leave Policy Reform

This paper reviews empirical studies that have examined the causal determinants of fertility behaviour. In particular, we compare the approaches adopted in the different disciplines to improve our understanding of how birth dynamics are influenced by changes in female employment and changes in family policies. The wide array of panel data that have become available in recent years provide great potential for advanced causal modelling in this field. Event history modelling has been a dominant approach in sociology and demography. However, researchers are increasingly turning to other methods to unravel causal effects, such as fixed-effects modelling, the regression discontinuity approach, and statistical matching. We summarise selected studies, and discuss the advantages and the shortcomings of the different approaches. In an empirical section, we analyse the impact of the German 2007 policy reform on birth behaviour to illustrate the difficulties involved in isolating policy effects. The final chapter concludes by underscoring that even simple modelling strategies may be beneficial for improving our understanding of how policy effects shape demographic behaviour, and for laying the groundwork for more fine-grained causal investigations.&#x0D; * This article belongs to a special issue on “Identification of causal mechanisms in demographic research: The contribution of panel data”.

Falsely diagnosed thyrotoxicosis caused by anti-streptavidin antibodies and pre-wash procedures

BackgroundAnti-streptavidin antibodies are causal determinants of analytical interference during Thyroid function tests, and numerous reports have detailed such interference, with anti-streptavidin antibodies attracting attention.Case presentationWe conducted a straightforward investigation of interference due to anti-streptavidin antibodies, with a case of a 60-year-old Japanese man who consulted our department for inconsistencies between his clinical course and Thyroid function tests. Experiments were conducted using Cobas8000 e602, which employs assay procedures with pre-wash to evaluate FT4 and FT3 levels.ConclusionsTo our knowledge, this is the first published report to clearly investigate such interferences using a combination of polyethylene glycol precipitation, heterophilic blocking tube precipitation, streptavidin-coated magnetic particle precipitation, and different instruments with or without pre-wash. Clinicians should consider that interferences caused by anti-streptavidin antibodies could lead to a misdiagnosis of thyrotoxicosis. Moreover, discussions between laboratory specialists, clinicians, and manufacturers are required to identify interferences and avoid unnecessary examinations and inappropriate treatment.

Association between secessionist tendencies and perceived intragroup conflict: implications of adherence to regionalist and essentialist beliefs

This study focuses on the relationship between secessionist tendencies, which are understood to be the desire of a set of certain individuals to cease being part of an ingroup in order to form a new class or identity, and perceived conflict within the original affiliation. The working hypothesis is that there is a positive correlation between these variables. Two hundred and twenty-four volunteer participants responded to five questionnaires that measured the main variables of this study and supplied feedback through other questionnaires related to social identity: regionalism (a form of ethnocentrism), group identification, and essentialism. The main results indicate that secessionism is positively associated with the perception of conflict between the ingroup and the superordinate ingroup, and that both variables in turn correlate with the other variables studied. The results are discussed in terms of the possible causal determination between the variables drawn from the aforementioned empirical evidence and the supporting theory.

The Genetic Basis of Hypertension

Hypertension (HTN) is one of the major risk factors for almost all cardiovascular diseases including coronary artery disease, stroke, heart failure and renal failure. Nonetheless , blood pressure (BP) regulation is insufficient due to its multifactorial nature involving interactions among genetic, environmental, mechanistic and neuroendocrine factors. Essential hypertension is the most frequent diagnosis indicating that a monocausal etiology has not been identified. The identification of causal genetic determinants has been unfulfilling. Analyses of rare monogenic syndromes of HTN focusing on renal sodium handling and steroid hormone metabolism have proved the well-defined genetic frame of hypertension though they do not affect the normal distribution of BP in the general population. Genome-wide association studies (GWAS) have revealed genetic variants that are associated with BP with small effect size which cumulatively explain to a very small extend the variability of BP. New large-scale studies in the genomic arena will clarify the polygenic determinants of BP and open a perspective on translation of the progression in BP genetics to clinical use.

Neurological Complications Acquired During Pediatric Critical Illness: Exploratory "Mixed Graphical Modeling" Analysis Using Serum Biomarker Levels.

Neurologic complications, consisting of the acute development of a neurologic disorder, that is, not present at admission but develops during the course of illness, can be difficult to detect in the PICU due to sedation, neuromuscular blockade, and young age. We evaluated the direct relationships of serum biomarkers and clinical variables to the development of neurologic complications. Analysis was performed using mixed graphical models, a machine learning approach that allows inference of cause-effect associations from continuous and discrete data. Secondary analysis of a previous prospective observational study. PICU, single quaternary-care center. Individuals admitted to the PICU, younger than18 years old, with intravascular access via an indwelling catheter. None. About 101 patients were included in this analysis. Serum (days 1-7) was analyzed for glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, and alpha-II spectrin breakdown product 150 utilizing enzyme-linked immunosorbent assays. Serum levels of neuron-specific enolase, myelin basic protein, and S100 calcium binding protein B used in these models were reported previously. Demographic data, use of selected clinical therapies, lengths of stay, and ancillary neurologic testing (head CT, brain MRI, and electroencephalogram) results were recorded. The Mixed Graphical Model-Fast-Causal Inference-Maximum algorithm was applied to the dataset. About 13 of 101 patients developed a neurologic complication during their critical illness. The mixed graphical model identified peak levels of the neuronal biomarker neuron-specific enolase and ubiquitin C-terminal hydrolase-L1, and the astrocyte biomarker glial fibrillary acidic protein to be the direct causal determinants for the development of a neurologic complication; in contrast, clinical variables including age, sex, length of stay, and primary neurologic diagnosis were not direct causal determinants. Graphical models that include biomarkers in addition to clinical data are promising methods to evaluate direct relationships in the development of neurologic complications in critically ill children. Future work is required to validate and refine these models further, to determine if they can be used to predict which patients are at risk for/or with early neurologic complications.

Phenome-wide screening of GWAS data reveals the complex causal architecture of obesity.

In the present study, we sought to identify causal relationships between obesity and other complex traits and conditions using a data-driven hypothesis-free approach that uses genetic data to infer causal associations. We leveraged available summary-based genetic data from genome-wide association studies on 1498 phenotypes and applied the latent causal variable method (LCV) between obesity and all traits. We identified 110 traits causally associated with obesity. Of those, 109 were causal outcomes of obesity, while only leg pain in calves was a causal determinant of obesity. Causal outcomes of obesity included 26 phenotypes associated with cardiovascular diseases, 22 anthropometric measurements, nine with the musculoskeletal system, nine with behavioural or lifestyle factors including loneliness or isolation, six with respiratory diseases, five with body bioelectric impedances, four with psychiatric phenotypes, four related to the nervous system, four with disabilities or long-standing illness, three with the gastrointestinal system, three with use of analgesics, two with metabolic diseases, one with inflammatory response and one with the neurodevelopmental disorder ADHD, among others. In particular, some causal outcomes of obesity included hypertension, stroke, ever having a period of extreme irritability, low forced vital capacity and forced expiratory volume, diseases of the musculoskeletal system, diabetes, carpal tunnel syndrome, loneliness or isolation, high leukocyte count, and ADHD. Our results indicate that obesity causally affects a wide range of traits and comorbid diseases, thus providing an overview of the metabolic, physiological, and neuropsychiatric impact of obesity on human health.

Fake news as a social phenomenon in the digital age: a sociological research agenda

This paper proposes a sociological research agenda for analysing the spreading mechanisms of misinformation in contemporary society. The contemporary fake news phenomenon is approached as an emergent outcome of inter-related technological, economic, socio-cultural and political factors that have made society vulnerable to misinformation. Those factors are understood as generators of various social dynamics rather than as direct causal determinants. In order to better acknowledge the conditions under which fake news is propagated and legitimated in digital society, news should be approached not only as a commodity that functions in a market-driven economy, but also as a social institution that regulates political discourse and public debate. Based on these considerations, the conclusions support the necessity of a more prominent sociological focus on media studies, which could build awareness of the performative role of language in the context of technologically mediated realities.

Adversarial orthogonal regression: Two non-linear regressions for causal inference

We propose two nonlinear regression methods, namely, Adversarial Orthogonal Regression (AdOR) for additive noise models and Adversarial Orthogonal Structural Equation Model (AdOSE) for the general case of structural equation models. Both methods try to make the residual of regression independent from regressors, while putting no assumption on noise distribution. In both methods, two adversarial networks are trained simultaneously where a regression network outputs predictions and a loss network that estimates mutual information (in AdOR) and KL-divergence (in AdOSE). These methods can be formulated as a minimax two-player game; at equilibrium, AdOR finds a deterministic map between inputs and output and estimates mutual information between residual and inputs, while AdOSE estimates a conditional probability distribution of output given inputs. The proposed methods can be used as subroutines to address several learning problems in causality, such as causal direction determination (or more generally, causal structure learning) and causal model estimation. Experimental results on both synthetic and real-world data demonstrate that the proposed methods have remarkable performance with respect to previous solutions.

Stratification of Type 2 Diabetes by Age of Diagnosis in the UK Biobank Reveals Subgroup-Specific Genetic Associations and Causal Risk Profiles.

The pathogenesis of type 2 diabetes (T2D) might change with increasing age. Here, we used a stratification based on age of diagnosis to gain insight into the genetics and causal risk factors of T2D across different age-groups. We performed genome-wide association studies (GWAS) on T2D and T2D subgroups based on age of diagnosis (<50, 50–60, 60–70, and >70 years) (total of 24,986 cases). As control subjects, participants were at least 70 years of age at the end of follow-up without developing T2D (N =187,130). GWAS identified 208 independent lead single nucleotide polymorphism (SNPs) mapping to 69 loci associated with T2D (P < 1.0e−8). Among others, SNPs mapped to CDKN2B-AS1 and multiple independent SNPs mapped to TCF7L2 were more strongly associated with cases diagnosed after age 70 years than with cases diagnosed before age 50 years. Based on the different case groups, we performed two-sample Mendelian randomization. Most notably, we observed that of the investigated risk factors, the association between BMI and T2D attenuated with increasing age of diagnosis. Collectively, our results indicate that stratification of T2D based on age of diag-nosis reveals subgroup-specific genetics and causal determinants, supporting the hypothesis that the pathogenesis of T2D changes with increasing age.

COMPORTAMENTO E GRAMÁTICA

In this article, Skinner’s radical behaviorism and Wittgenstein’s conceptions of meaning are approached in view of two questions related to subjective states and causal determination of behavior. The confrontation of both conceptions expresses agreement in rejecting referentialism and mentalism, as in the human behavior emphasis. However, the superficial agreement hides a tension between the normative and the empirical, in which there is radical disagreement. While Wittgenstein emphasizes the organizative character of the grammar that rules language, Skinner takes it as mere generalization of empirical contingencies, which produces different notions of behavior.

595 The associations between excessive daytime sleepiness and emotional lability in typically developing adolescents

Abstract Introduction Excessive daytime sleepiness (EDS), defined as a tendency to fall asleep unintentionally during the day, and emotional lability, characterized by emotional outbursts and quick changes in mood, are prevalent amongst adolescents. They contribute to functional impairments and are inter-related, but are frequently investigated independently. In addition, sleep duration is related to both EDS and emotional/behavioral regulation, but previous studies did not take this into account. The aim of this study was to characterize the associations between emotional lability, impulsivity and EDS in adolescents while controlling for objectively measured sleep duration. It was hypothesized that higher levels of EDS in adolescents would be associated with higher levels of emotional lability and impulsivity in adolescents above and beyond the impact of sleep duration. Methods Participants included 52 typically developing adolescents (38 females) aged 11 to 16 years old (Mean age = 13.10 years, SD = 1.59). EDS was measured using the Sleep Disorders Inventory for Students. Emotional lability and impulsivity were measured using the Conners Global Index Scale. Sleep was measured using actigraphy and sleep logs. Results Parallel multiple regression analyses were conducted with EDS as the independent variable, and emotional lability or impulsivity as the dependent variables, while controlling for age, gender, bedtime, waketimes, and sleep duration. These analyses revealed significant positive association between EDS and emotional lability such that adolescents with high levels of EDS also presented with high levels of emotional lability (F(6, 51) = 4.631, p = &amp;lt; .001, β =.62, p = &amp;lt;.001). There were no significant associations found between EDS and impulsivity. Conclusion This study found that EDS was associated with emotional, but not behavioral, dysregulation in adolescents. Interventions aimed at reducing EDS and at improving adolescents’ emotional regulation should be considered as a means to optimize adolescents’ daytime functioning. Limitations of the current study include the use of a cross-sectional design that does not permit determination of causality. Future research should be conducted to better understand the mechanisms underlying the interplay between EDS and daytime functioning of adolescents. Support (if any):

Systematic review of the association between long-term exposure to fine particulate matter and mortality

ABSTRACT We used a transparent systematic review framework based on best practices for evaluating study quality and integrating evidence to conduct a review of the available epidemiology studies evaluating associations between long-term exposure to ambient concentrations of PM2.5 and mortality (all-cause and non-accidental) conducted in North America. We found that while there is some consistency across studies for reporting positive associations, these associations are weak and several important methodological issues have led to uncertainties with regard to the evidence from these studies, including potential confounding by measured and unmeasured factors, exposue measurement error, and model misspecification. These uncertainties provide a plausible, alternative explanation to causality for the weakly positive findings across studies. Using a causality framework that incorporates best practices for making causal determinations, we concluded that the evidence for a causal relationship between long-term exposure to ambient PM2.5 concentrations and mortality from these studies is inadequate.

Complexities surrounding the diagnosis and management of hypercalcaemia in pregnancy.

SummaryHypercalcaemia in pregnancy is uncommon, with associated adverse obstetric and perinatal outcomes for both the mother and the fetus. Determination of causality is central to its management. Diagnostic imaging techniques are limited during pregnancy and the diagnosis is made more complex by physiological changes in calcium and vitamin D homeostasis in pregnancy. Further, therapeutic options are limited due to safety considerations for the pregnant woman and the developing foetus. Three cases of hypercalcaemia in pregnancy will be presented, highlighting the distinct aetiologies and management strategies for hypercalcaemia in pregnancy and the importance of early measurement of serum calcium in pregnancy screening.Learning pointsThere are complex physiological changes in calcium balance in pregnancy, including increased calcium intestinal absorption and renal excretion.Hypercalcaemia in pregnancy is uncommon but has important potential maternal and foetal complications, making a compelling argument for routine antenatal, calcium screening.Identifying the cause of hypercalcaemia in pregnancy can be challenging due to the complex placental interplay in biochemical test interpretation and due to safety constraints restricting imaging and surgery.Acute medical management of hypercalcaemia must be considered in the context of both maternal and foetal well-being, along with gestational age and specific consideration for the safety of the developing fetus in late gestation.

Abolition of the obligation to cease an occupation for acknowledgment of an occupational skin disease: Backgrounds and perspectives.

The occupational disease skin No.5101 ("severe or recurrent skin diseases that have forced the patient to refrain from all activities that were or could be the cause of the development, aggravation or resurgence of the disease") is the most frequently notified occupational disease in Germany. Since 1936, the medical-objective obligation to refrain from risky work activities, which has been necessary for the recognition of this occupational disease, was intended to delimit trivial diseases, facilitate the determination of occupational causality and promote prevention. The abolition of the legal obligation to refrain from risky work activities as a criterion for the recognition of the occupational disease 5101 as of 01.01.2021 has significant effects on the occupational dermatological care and expert assessment of this occupational disease. For less severe occupational skin diseases, however, the preventive dermatologist's procedure established since 1972 will continue to apply.