Experimentation in cosmology: Intervening on the whole universe.

There are many arguments against the possibility of experimenting on the whole universe. This system seems to be too big to be manipulated, it exists in only one exemplar and its evolution is a non-repeatable process. In this paper, I claim that we can nonetheless talk about experimentation in cosmology if we use Woodward's non-anthropocentric notion of intervention. However, Woodward and other interventionists argued that an intervention was necessarily an exogenous causal process and thus that no intervention on a closed system such as the universe was possible. I discuss their argument and I determine the conditions under which a consistent notion of endogenous intervention on the universe can be defined. Then, I show that there is at least one cosmic phenomenon satisfying these conditions: the photon decoupling. Finally, I draw some conclusions from this analysis regarding a realist approach of cosmology.

Developing improved crash prevention approaches through in-depth investigation of motorcycle crash causation patterns.

Despite advancements in road safety, Powered Two-Wheelers (PTWs) remain a vulnerable group with disproportionately high crash rates. This paper presents an in-depth analysis of PTW crashes in six European countries, with a case study of Loss of Control in Curves (LoCC), to address the gap between crash causation and prevention. By examining crash causation factors and their linkage to prevention strategies, the study illustrates various approaches for connecting causes and countermeasures. These approaches, which are applicable to different crash scenarios, include looking forward in the crash causation chains, looking backward, looking at only the last cause (critical events), or the first cause, or following a systemic approach. The research introduces a set of guidelines following the safe system approach, aiming to enhance the understanding of crash prevention among policymakers. The systemic approach to countermeasures, bridges the shortcomings of traditional crash causation studies that may exhibit bias or a narrow focus on "root causes". The proposed approach emphasizes the need for a comprehensive view of crash scenarios (i.e., considering the entire crash causation chain or multiple causation chains) and ensuring that preventive measures address the full spectrum of the system. It also takes in to account external factors such as cost, benefits, and politics, leading to improved road safety outcomes. The study findings are significant for researchers, since it is a step forward in in-depth crash causation studies, as well as road practitioners and policymakers, in providing a strategic framework for more effective and efficient road safety interventions.

Lithium in Drinking Water and its Potential Impact on Mental Health: A Review.

This review explores the relationship between lithium in drinking water and mental health, a subject that has garnered increasing attention in investigations. Lithium, a metal with a well-established role in psychiatric medications, is found in trace amounts in drinking water, and studies suggest its potential correlations with lower rates of suicide and certain psychiatric disorders. However, these correlations do not imply causation, necessitating an examination of the underlying mechanisms. Lithium concentrations in drinking water vary globally, presenting challenges in establishing a universal threshold for "high" or "low" levels. Additionally, the optimal dosage for potential mental health benefits remains uncertain. Lithium is not considered an essential nutrient, and supplementation should be approached with caution due to possible toxicity risks, emphasizing the importance of medical supervision. The lack of causation and ongoing need for further investigation underscores the importance of cautious interpretation and transparent communication in navigating this evolving field.

Bullying victimization and bullying perpetration, social anxiety, and social withdrawal in Portuguese adolescents: A reciprocal association model.

Further research is needed to clarify the association of the different forms of bullying with social anxiety and social withdrawal over time in adolescents. This two-wave panel study with a 1-year time lag (October 2021-October 2022) examined the cross-lagged relationships between bullying victimization and bullying perpetration, social anxiety (i.e., fear or distress in social situations), and social withdrawal (i.e., consistent, and deliberate social solitude). Participants were 485 middle school students (234 girls) attending the seventh or eighth grade at Time 1 (T1) (Mage = 12.67 years, SD = 1.14 years). Social anxiety and social withdrawal were assessed using subscales of the Social and Emotional Competencies Evaluation Questionnaire. Bullying perpetration and bullying victimization were assessed using the Bullying and Cyberbullying Behavior Questionnaire-Short Form. The within-wave associations between the study variables were similar at T1 and Time 2 (T2), with the exception that the association between bullying perpetration and social anxiety was much weaker at T1 than at T2. The results of the path analysis showed that T1 bullying perpetration predicted T2 social anxiety, and that T1 bullying victimization predicted T2 social withdrawal. We also found a reciprocal relationship between social anxiety and social withdrawal. These findings highlight the importance of preventive and remediation interventions to reduce social anxiety in adolescents who engage in and experience bullying behavior.

Navigating causal reasoning in sustainability science.

When reasoning about causes of sustainability problems and possible solutions, sustainability scientists rely on disciplinary-based understanding of cause-effect relations. These disciplinary assumptions enable and constrain how causal knowledge is generated, yet they are rarely made explicit. In a multidisciplinary field like sustainability science, lack of understanding differences in causal reasoning impedes our ability to address complex sustainability problems. To support navigating the diversity of causal reasoning, we articulate when and how during a research process researchers engage in causal reasoning and discuss four common ideas about causation that direct it. This articulation provides guidance for researchers to make their own assumptions and choices transparent and to interpret other researchers' approaches. Understanding how causal claims are made and justified enables sustainability researchers to evaluate the diversity of causal claims, to build collaborations across disciplines, and to assess whether proposed solutions are suitable for a given problem.

Association between glaucoma and stroke: A bidirectional mendelian randomization study.

Purpose: Observational studies have reported positive associations between glaucoma and stroke; however, controversial results exist. Importantly, the nature of the relationship remains unknown since previous studies were not designed to test causality. Therefore, we aimed to investigate the possible causal relationships between glaucoma and stroke. Methods: Our two-sample Mendelian randomization (MR) encompassed multi-ethnic large-scale genome-wide association studies with more than 20000 cases and 260000 controls for glaucoma, and more than 80000 cases and 630000 controls for stroke. Individual effect estimates for each SNP were combined using the inverse-variance weighted (IVW) method. To avoid potential pleiotropic effects, we adjusted the main results by excluding genetic variants associated with metabolic factors. The weighted median and MR-Egger methods were also used for the sensitivity analysis. Results: Our MR analysis revealed that glaucoma and its subtypes, including primary open-angle glaucoma and primary angle-closure glaucoma, exhibited no causal role in relation to any stroke (AS), any ischemic stroke (AIS), large-artery atherosclerotic stroke (LAS), small-vessel stroke (SVS), or cardioembolic stroke (CES) across MR analyses (all P â€‹> â€‹0.05). The null associations remained robust even after adjusting for metabolic-related traits and were consistent in both the European and Asian populations. Furthermore, reverse MR analyses also did not indicate any significant causal effects of AS, AIS, LAS, or CES on glaucoma risk. Conclusions: Evidence from our series of causal inference approaches using large-scale population-based MR analyses did not support causal effects between glaucoma and stroke. These findings suggest that the relationship of glaucoma management and stroke risk prevention should be carefully evaluated in future studies. In turn, stroke diagnosis should not be simply applied to glaucoma risk prediction.

Is evidence-based practice justified?-A philosophical critique.

BACKGROUND: Evidence-based practice is the principle governing a range of healthcare practices and beyond. However, it has suffered from a lack of philosophical rigour. This paper sets out to analyse the epistemological basis of evidence-based practice. METHOD: The paper uses a conceptual analysis. First, it describes the implicit epistemology at work in evidence-based practice. Second, it evaluates the implicit epistemological basis. RESULTS: The analysis indicates that evidence-based practice lacks an explicit epistemological basis. It shows, moreover, that the implicit epistemological basis is untenable. CONCLUSION: There is a need to re-think the epistemological basis for evidence-based practice. Evidence-based practice is out of touch with developments within philosophy of science.

The relationship between psoriasis and vitiligo: From a comprehensive study.

BACKGROUND: Both psoriasis and vitiligo are autoimmune skin diseases. Previous observational studies have indicated a relationship between the two conditions, and simultaneous onset of both diseases poses increased health risks to patients. However, limited research has explored the causal relationship between psoriasis and vitiligo. OBJECTIVES: To investigate whether a causal association exists between psoriasis and vitiligo. METHODS: A case of Chinese patients diagnosed with psoriasis and vitiligo has been reported. Transcriptome sequencing was performed on normal, psoriasis, vitiligo, and co-morbid skin tissues of the patients, and single-cell transcriptome sequencing was conducted on the co-morbid skin tissues. A comprehensive Mendelian randomization analysis of Genome-wide association studies (GWAS) was performed on a cohort of 261 018 European individuals with psoriasis from the IEU Open GWAS Project and vitiligo from the National Institutes of Health (NIH) Database of Genotypes and Phenotypes. RESULTS: Case report and transcriptome results showed that skin tissue with vitiligo combined with psoriasis exhibited both vitiligo and psoriasis. Single-cell transcriptome sequencing results showed that in comparison to normal skin and psoriatic skin, the proportions of CD8+ T cells, natural killer cells, naive T cells, T helper cells 17, regulatory T cells, conventional type 1 dendritic cells, Conventional type 2 dendritic cells, and plasmacytoid dendritic cells were all increased in skin tissue with vitiligo combined with psoriasis. Mendelian randomization analysis included 4510 patients with psoriasis and 4680 patients with vitiligo. The results showed no causal relationship between vitiligo and psoriasis in the forward direction (p = 0.192; odds ratio [OR], 1.059; 95% confidence interval [CI], 0.971-1.155) or in the reverse direction (p = 0.459; OR, 0.927; 95% CI, 0.757-1.134). CONCLUSIONS: This study suggests that the association between psoriasis and vitiligo may be closely related to immunity, however, Mendelian randomization studies do not support a causal relationship. These findings hold significant implications for clinicians aiming to enhance their understanding and treatment approaches for psoriasis and vitiligo.

Semiparametric g-computation for survival outcomes with time-fixed exposures: An illustration.

PURPOSE: Generalized (g-) computation is a useful tool for causal inference in epidemiology. However, in settings when the outcome is a survival time subject to right censoring, the standard pooled logistic regression approach to g-computation requires arbitrary discretization of time, parametric modeling of the baseline hazard function, and the need to expand one's dataset. We illustrate a semiparametric Breslow estimator for g-computation with time-fixed treatments and survival outcomes that is not subject to these limitations. METHODS: We compare performance of the Breslow g-computation estimator to the pooled logistic g-computation estimator in simulations and illustrate both approaches to estimate the effect of a 3-drug vs 2-drug antiretroviral therapy regimen among people with HIV. RESULTS: In simulations, both approaches performed well at the end of follow-up. The pooled logistic approach was biased at times between the endpoints of the discrete time intervals used, while the Breslow approach was not. In the example, both approaches estimated a 1-year risk difference of about 6 % in favor of the 3-drug regimen, but the shape of the survival curves differed. CONCLUSIONS: The Breslow g-computation estimator of counterfactual risk functions does not rely on strong parametric assumptions about the time-to-event distribution or onerous dataset expansions.

On Persons, Populations, and Causal Mechanisms Some Critical Reflections on Lundh (2023).

While agreeing with Lundh (2023) on many of his major points, this article also questions the notion of a 'population psychology.' It is argued that the knowledge produced in population-level studies, whether correlational, experimental, or mixed, is inherently demographic in nature. Concerning individual-level studies, agreement with Lundh (2023) is expressed concerning the need to distinguish between a conception of individuals as mere depositories of neurophysiological mechanisms on the one hand, and as active, purposeful agents on the other. It is suggested that the conceptual framework called 'critical personalism' would well serve a scientific psychology committed to the latter view.

What question are we trying to answer? Embracing causal inference.

This study summarizes a presentation at the symposium for the Calvin Schwabe Award for Lifetime Achievement in Veterinary Epidemiology and Preventive Medicine, which was awarded to the first author. As epidemiologists, we are taught that "correlation does not imply causation." While true, identifying causes is a key objective for much of the research that we conduct. There is empirical evidence that veterinary epidemiologists are conducting observational research with the intent to identify causes; many studies include control for confounding variables, and causal language is often used when interpreting study results. Frameworks for studying causes include the articulation of specific hypotheses to be tested, approaches for the selection of variables, methods for statistical estimation of the relationship between the exposure and the outcome, and interpretation of that relationship as causal. When comparing observational studies in veterinary populations to those conducted in human populations, the application of each of these steps differs substantially. The a priori identification of exposure-outcome pairs of interest are less common in observational studies in the veterinary literature compared to the human literature, and prior knowledge is used to select confounding variables in most observational studies in human populations, whereas data-driven approaches are the norm in veterinary populations. The consequences of not having a defined exposure-outcome hypotheses of interest and using data-driven analytical approaches include an increased probability of biased results and poor replicability of results. A discussion by the community of researchers on current approaches to studying causes in observational studies in veterinary populations is warranted.

Cervical Spine Manipulation and Causation of Cervical Artery Dissection: A Review of 10 Case Reports.

Recent media coverage of high-profile cases of cervical artery dissection (CAD) has ignited the discussion about the role of cervical spine manipulation (CSM) in causing cervical artery dissection. However, research does not support a causal association between cervical spine manipulation and cervical artery dissection in a healthy cervical spine. The objective of this study was to review the 10 most recent case reports of cervical spine manipulation and cervical artery dissection for convincing evidence of the causation of cervical artery dissection by cervical spine manipulation. Nine of 10 case reports showed no convincing evidence of a causal relationship between cervical spine manipulation and cervical artery dissection. The 10th case report was exceptional as the CSM was contraindicated by pre-existing cervical spine pathology. We conclude that these 10 case reports provide no convincing evidence of the causation of cervical artery dissection by cervical spine manipulation in a healthy cervical spine. One case report demonstrated that cervical spine manipulation can cause cervical artery dissection when performed in the presence of pre-existing cervical spine pathology. Therefore, we conclude that practitioners should exclude cervical spine pathology before performing cervical spine manipulation.

A Note on Modelling Bidirectional Feedback Loops in Mendelian Randomization Studies.

Structural equation models (SEMs) involving feedback loops may offer advantages over standard instrumental variables estimators in terms of modelling causal effects in the presence of bidirectional relationships. In the following note, we show that in the case of a single "exposure" and "outcome" variable, modelling relationships using a SEM with a simple bidirectional linear feedback loop offers no advantage over traditional instrumental variables estimators in terms of consistency (i.e. both approaches yield consistent estimates of the causal effect, provided that causal estimates are obtained in both directions). In the case of finite samples, traditional IV estimators and SEM exhibited similar power across many of the conditions we examined, although which method performed best depended on the residual correlation between variables and the strength of the instruments. In particular, the power of SEM was insensitive to the residual correlation between variables, whereas the power of the Wald estimator/2SLS improved (deteriorated) relative to SEM as the magnitude of the residual correlation increased (decreased) assuming a positive causal effect of the exposure on the outcome. The power of SEM improved relative to the Wald estimator/2SLS as the instruments explained more residual variance in the "outcome" variable.

[Incapacity to work due to mental disorders-economic, individual, and treatment-specific aspects]. / Arbeitsunfähigkeit bei psychischen Störungen ­ ökonomische, individuelle und behandlungsspezifische Aspekte.

The changes in the modern work environment are accompanied by specific stressors that can have a negative impact on employees' mental health. In line with this, the proportion of sick-leave days due to mental disorders has recently risen to 17.7% compared to 10.9% in 2007, which in 2021 was associated with costs of 42.9 billion euros due to losses of gross value and productivity.Based on current health economic studies, this review provides an overview of the economic impact of incapacity to work and early retirement due to various mental disorders in Germany. In absolute figures, expenditure on incapacity to work is particularly high for common mental illnesses such as affective and anxiety disorders. Rarer mental disorders such as post-traumatic stress disorder and eating disorders cause high costs in relation to their low prevalence, particularly due to sickness benefit payments.In addition to these economic implications, the consequences of incapacity to work, early retirement, and unemployment are examined at an individual level and explanatory approaches for the specific psychosocial stresses are presented. The latter highlights the need for scientifically substantiated treatment methods. Certified treatments have proven to be efficient in reducing the number of sick-leave days, particularly for common mental disorders. This applies even more to workplace-related interventions, which appear to be superior to conventional methods in this respect. Workplace-based therapies incorporate work-related models and focus on the planning of reintegration into the workplace. Further naturalistic studies are needed to test the transferability of the effectiveness of these treatments to other disorders.

Interventional probability of causation (IPoC) with epidemiological and partial mechanistic evidence: benzene vs. formaldehyde and acute myeloid leukemia (AML).

INTRODUCTION: Causal epidemiology for regulatory risk analysis seeks to evaluate how removing or reducing exposures would change disease occurrence rates. We define interventional probability of causation (IPoC) as the change in probability of a disease (or other harm) occurring over a lifetime or other specified time interval that would be caused by a specified change in exposure, as predicted by a fully specified causal model. We define the closely related concept of causal assigned share (CAS) as the predicted fraction of disease risk that would be removed or prevented by a specified reduction in exposure, holding other variables fixed. Traditional approaches used to evaluate the preventable risk implications of epidemiological associations, including population attributable fraction (PAF) and the Bradford Hill considerations, cannot reveal whether removing a risk factor would reduce disease incidence. We argue that modern formal causal models coupled with causal artificial intelligence (CAI) and realistically partial and imperfect knowledge of underlying disease mechanisms, show great promise for determining and quantifying IPoC and CAS for exposures and diseases of practical interest. METHODS: We briefly review key CAI concepts and terms and then apply them to define IPoC and CAS. We present steps to quantify IPoC using a fully specified causal Bayesian network (BN) model. Useful bounds for quantitative IPoC and CAS calculations are derived for a two-stage clonal expansion (TSCE) model for carcinogenesis and illustrated by applying them to benzene and formaldehyde based on available epidemiological and partial mechanistic evidence. RESULTS: Causal BN models for benzene and risk of acute myeloid leukemia (AML) incorporating mechanistic, toxicological and epidemiological findings show that prolonged high-intensity exposure to benzene can increase risk of AML (IPoC of up to 7e-5, CAS of up to 54%). By contrast, no causal pathway leading from formaldehyde exposure to increased risk of AML was identified, consistent with much previous mechanistic, toxicological and epidemiological evidence; therefore, the IPoC and CAS for formaldehyde-induced AML are likely to be zero. CONCLUSION: We conclude that the IPoC approach can differentiate between likely and unlikely causal factors and can provide useful upper bounds for IPoC and CAS for some exposures and diseases of practical importance. For causal factors, IPoC can help to estimate the quantitative impacts on health risks of reducing exposures, even in situations where mechanistic evidence is realistically incomplete and individual-level exposure-response parameters are uncertain. This illustrates the strength that can be gained for causal inference by using causal models to generate testable hypotheses and then obtaining toxicological data to test the hypotheses implied by the models-and, where necessary, refine the models. This virtuous cycle provides additional insight into causal determinations that may not be available from weight-of-evidence considerations alone.

Alzheimer's disease and oral manifestations: a bi-directional Mendelian randomization study.

Background: Epidemiological studies have provided evidence suggesting an association between Alzheimer's disease (AD) and various oral manifestations. However, conflicting conclusions have been drawn, and whether a causal association truly exists remains unclear. Methods: In order to investigate the potential causal association between AD and prevalent oral diseases, we conducted a bi-directional two-sample Mendelian randomization analysis based on summary statistics from genome-wide association studies of AD (N = 63,926), as well as mouth ulcer (N = 461,103), oral cavity cancer (N = 4,151), and periodontal disease (N = 527,652). Results: We identified that one standard increase in the risk of AD was causally associated with a reduced risk of oral cavity cancer (OR = 0.76, 95% CI: 0.63-0.92, p = 3.73 × 10-3). In the opposite direction, oral conditions were not causally associated with risk of AD. Conclusion: The present findings contributed to a better understanding of the correlation between AD and oral conditions, specifically oral cavity cancer. These results also identified new avenues for exploring the underlying mechanisms of oral cavity cancer.

The cell as a semiotic system that realizes closure to efficient causation: The semiotic (M, R) system.

Robert Rosen defines organisms as material systems closed to efficient causation, and proposes the replicative (M, R) system as a model for them. Recently, we presented a cell model that realizes Rosen's formal model, based on Hofmeyr's analysis of the functional organization of cell biochemistry and on Rosen's construction of the replication function. In this article we propose a cell model that, starting from the same biochemical processes, replaces the replication function with a set of semiotic relations between some of the elements that participate in cellular processes. The result is a cell model that constitutes a semiotic system that realizes closure to efficient causation: a semiotic (M, R) system. We compare the models of closure that correspond to the replicative (M, R) system and the semiotic (M, R) system. Additionally, we discuss the role that the genetic code and protein synthesis play in the semiotic closure to efficient causation. Finally, we outline the method to extend this analysis to more complex organisms.

R.A. Fisher, indeterminism, and the fundamental theorem of natural selection.

This paper is about the relationship between R.A. Fisher's fundamental theorem of natural selection (FTNS) and the two major pieces that Fisher wrote on indeterminism, "Indeterminism and Natural Selection" (1934) and Creative Aspects of Natural Law (1950). I argue that the FTNS presents a picture of natural selection that is interestingly different from what we find in these two indeterminism pieces, pace some recent work that advances the opposite conclusion. I also identify as the source of this difference both the mathematical form of the FTNS (i.e., a differential equation) and Fisher's meta-scientific commitment to advancing "general" claims about evolution.

Central Causation of Autism/ASDs via Excessive [Ca2+]i Impacting Six Mechanisms Controlling Synaptogenesis during the Perinatal Period: The Role of Electromagnetic Fields and Chemicals and the NO/ONOO(-) Cycle, as Well as Specific Mutations.

The roles of perinatal development, intracellular calcium [Ca2+]i, and synaptogenesis disruption are not novel in the autism/ASD literature. The focus on six mechanisms controlling synaptogenesis, each regulated by [Ca2+]i, and each aberrant in ASDs is novel. The model presented here predicts that autism epidemic causation involves central roles of both electromagnetic fields (EMFs) and chemicals. EMFs act via voltage-gated calcium channel (VGCC) activation and [Ca2+]i elevation. A total of 15 autism-implicated chemical classes each act to produce [Ca2+]i elevation, 12 acting via NMDA receptor activation, and three acting via other mechanisms. The chronic nature of ASDs is explained via NO/ONOO(-) vicious cycle elevation and MeCP2 epigenetic dysfunction. Genetic causation often also involves [Ca2+]i elevation or other impacts on synaptogenesis. The literature examining each of these steps is systematically examined and found to be consistent with predictions. Approaches that may be sed for ASD prevention or treatment are discussed in connection with this special issue: The current situation and prospects for children with ASDs. Such approaches include EMF, chemical avoidance, and using nutrients and other agents to raise the levels of Nrf2. An enriched environment, vitamin D, magnesium, and omega-3s in fish oil may also be helpful.